Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Toyohira, Yumiko; Horisita, Takafumi; Satoh, Noriaki; Takahashi, Keita; Zhang, Han; Iinuma, Munekazu; Yoshinaga, Yukari; Ueno, Susumu; Tsutsui, Masato; Sata, Takeyoshi; Yanagihara, Nobuyuki

2015-12-01

Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

PubMed

Clyman, Ronald I; Wickremasinghe, Andrea; Merritt, T Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M; Attridge, Joshua T; Swanson, Jonathan R; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J

2014-06-01

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 μg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [μg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones

PubMed Central

Clyman, Ronald I.; Wickremasinghe, Andrea; Merritt, T. Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M.; Attridge, Joshua T.; Swanson, Jonathan R.; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J.

2014-01-01

Objective To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. Study design We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. Results Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Conclusion Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. PMID:24636853

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

PubMed

Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

2015-10-01

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The effect of salts on catecholamine fluxes and adenosine triphosphatase activity in storage vesicles from the adrenal medulla

PubMed Central

Taugner, G.

1971-01-01

1. Influx and efflux of catecholamine and adenosine triphosphatase activity in storage vesicles from the adrenal medulla were studied with dl-[14C]adrenaline in different media. 2. The lowest values for flux and adenosine triphosphatase activity were observed in sucrose media in which an ATP-dependent influx of catecholamine compensated for an efflux of the same magnitude. Efflux in the presence or absence of ATP was similar. 3. In media containing sodium succinate or glutarate adenosine triphosphatase activity was higher and the ATP-dependent influx of catecholamine was about twice that observed in iso-osmotic sucrose medium. In the presence of ATP influx and efflux of catecholamine were balanced; in its absence there was a net release of catecholamine, since efflux was more than twice the influx. Efflux in the presence or absence of ATP was similar. 4. In media containing sodium or potassium chloride and in the presence of ATP influx and adenosine triphosphatase activity were further enhanced, but in the absence of ATP there was no further increase in influx, since catecholamine was released with or without ATP at the same rate. Efflux was therefore twice as high in the presence of ATP as in its absence. 5. Sodium nitrate suppressed the ATP-dependent influx nearly completely, but caused a greatly enhanced efflux, which was twice as high in the presence of ATP as in its absence. 6. The extinction of vesicular suspensions remained unchanged in the presence of ATP under conditions where the catecholamine efflux was balanced by the influx. Under conditions where the efflux was not compensated by influx, the extinction of the suspensions decreased in the presence of ATP more than in its absence. PMID:4256794

Catecholamines - urine

MedlinePlus

Dopamine - urine test; Epinephrine - urine test; Adrenalin - urine test; Urine metanephrine; Normetanephrine; Norepinephrine - urine test; Urine catecholamines; VMA; HVA; Metanephrine; Homovanillic ...

Aortoarteritis: Could it be a form of catecholamine-induced vasculitis?

PubMed Central

Sarathi, Vijaya; Lila, Anurag R.; Bandgar, Tushar R.; Shah, Nalini S.

2013-01-01

Catecholamine-induced vasculitis is a well known but rarely described entity. However, aortoarteritis as a manifestation of catecholamine-induced vasculitis is not described in the literature. We have reported two patients in whom pheochromocytoma coexisted with aortoarteritis. Both patients were young females with history of bilateral pheochromocytomas in more than one first-degree relative. Both patients also had bilateral adrenal pheochromocytomas (second patient also had paraganglioma at left renal hilum) with elevation of plasma free normetanephrine levels. We conclude that there may be an association between pheochromocytoma and aortoarteritis, and that catecholamine excess may have a role in the etiopathogenesis of aortoarteritis in these patients. PMID:23776874

Consideration of the degree of increase in urine metadrenalines provides superior specificity in the diagnosis of phaeochromocytoma than additional urine catecholamine measurement.

PubMed

Scargill, J J; Reed, P; Kane, J

2013-01-01

Measurement of fractionated plasma or urine metadrenalines is the recommended screening test in the diagnosis of phaeochromocytoma, with clinical cut-offs geared towards diagnostic sensitivity. Current practice at Salford Royal Hospital is to add urine catecholamines onto samples with raised urine metadrenalines, with the aim of adding specificity to a diagnosis of phaeochromocytoma. This practice was reviewed by identifying a series of patients with raised urine metadrenalines who had catecholamines reflectively added. A total of 358 samples were identified from 242 patients, of which 228 had urine catecholamines measured. A diagnosis of 'phaeochromocytoma' (n = 41) or 'no phaeochromocytoma' (n = 90) was obtained in 131 of 228 patients, giving raised urine metadrenalines a positive predictive value for phaeochromocytoma of 31%. The finding of increased urine catecholamines in samples with raised urine metadrenalines increased specificity for phaeochromocytoma to 70%. However, 95% diagnostic specificity for phaeochromocytoma could be achieved by the introduction of a second cut-off for urine metadrenalines geared towards maximizing specificity. Consideration of the degree of increase in urine metadrenalines is a superior method of determining the likelihood of phaeochromocytoma than measurement of urine catecholamines.

Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

PubMed

Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

2017-02-01

Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach

PubMed Central

Challis, B G; Pitfield, D; Mahroof, R M; Jamieson, N; Bhagra, C J; Vuylsteke, A; Pettit, S J; Chatterjee, K C

2017-01-01

A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases. Here, we report the case of a 38-year-old lady who presented with an acute Takotsubo or stress cardiomyopathy and catecholamine crisis, caused by an occult left-sided 5 cm PC. The initial presenting crisis manifested with symptoms of severe headache and abdominal pain, triggered by a respiratory tract infection. On admission to hospital, the patient rapidly deteriorated, developing respiratory failure, cardiogenic shock and subsequent cardiovascular collapse due to further exacerbation of the catecholamine crisis caused by a combination of opiates and intravenous corticosteroid. An echocardiogram revealed left ventricular apical hypokinesia and ballooning, with an estimated left ventricular ejection fraction of 10–15%. Herein, we outline the early stabilisation period, preoperative optimisation and intraoperative management, providing anecdotal guidance for the management of this rare life-threatening complication of PC. Learning points: A diagnosis of phaeochromocytoma should be considered in patients presenting with acute cardiomyopathy or cardiogenic shock without a clear ischaemic or valvular aetiology. Catecholamine crisis is a life-threatening medical emergency that requires cross-disciplinary expertise and management to ensure the best clinical outcome. After initial resuscitation, treatment of acute catecholamine-induced stress cardiomyopathy requires careful introduction of alpha-blockade followed by beta-blockade if necessary to manage β-receptor-mediated tachycardia. Prolonged α-adrenergic receptor stimulation by high levels of circulating catecholamines precipitates arterial vasoconstriction and intravascular volume contraction, which can further exacerbate hypotension. Invasive pressure monitoring can aid management of intravascular volume in these complex patients. PMID:29147570

Catecholamines and in vitro growth of pathogenic bacteria: enhancement of growth varies greatly among bacterial species

NASA Technical Reports Server (NTRS)

Belay, Tesfaye; Aviles, Hernan; Vance, Monique; Fountain, Kimberly; Sonnenfeld, Gerald

2003-01-01

The purpose of this study was to examine the effects of catecholamines on in vitro growth of a range of bacterial species, including anaerobes. Bacteria tested included: Porphyromonas gingivalis, Bacteriodes fragilis, Shigella boydii, Shigella sonnie, Enterobacter Sp, and Salmonella choleraesuis. The results of the current study indicated that supplementation of bacterial cultures in minimal medium with norepinephrine or epinephrine did not result in increased growth of bacteria. Positive controls involving treatment of Escherichia coli with catecholamines did result in increased growth of that bacterial species. The results of the present study extend previous observations that showed differential capability of catecholamines to enhance bacterial growth in vitro.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

PubMed

Spasojevic, Natasa; Jovanovic, Predrag; Dronjak, Sladjana

2015-03-01

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Plasma free metanephrines are superior to urine and plasma catecholamines and urine catecholamine metabolites for the investigation of phaeochromocytoma.

PubMed

Hickman, Peter E; Leong, Michelle; Chang, Julia; Wilson, Susan R; McWhinney, Brett

2009-02-01

To compare the relative diagnostic efficacy of several different tests used to establish a diagnosis of phaeochromocytoma, in patients with a proven diagnosis of phaeochromocytoma, and in hospital patients with significant disease of other types. We prospectively compared biochemical markers of catecholamine output and metabolism in plasma and urine in 22 patients with histologically proven phaeochromocytoma, 15 intensive care unit (ICU) patients, 30 patients on chronic haemodialysis and both hypertensive (n = 10) and normotensive (n = 16) controls. Receiver operating characteristic curves were plotted. At the point of maximum efficiency, plasma free metanephrines showed 100% sensitivity and 97.6% specificity, compared with plasma catecholamines (78.6% and 70.7%), urine catecholamines (78.6% and 87.8%), urine metanephrines (85.7% and 95.1%), and urine hydroxymethoxymandelic acid (HMMA or VMA) (93.0% and 75.8%). All patients with phaeochromocytoma had plasma free metanephrine concentrations at least 27% above the upper limit of the reference range. Only three other patients (two on haemodialysis and one in ICU) had PFM concentrations more than 50% above the upper limit of the reference range. In patients with phaeochromocytoma, plasma free metanephrines displayed superior diagnostic sensitivity and specificity compared with other biochemical markers of catecholamine output and metabolism.

Reactivity of catecholamine-driven Fenton reaction and its relationships with iron(III) speciation.

PubMed

Melin, Victoria; Henríquez, Adolfo; Freer, Juanita; Contreras, David

2015-03-01

Fenton reaction is the main source of free radicals in biological systems. The reactivity of this reaction can be modified by several factors, among these iron ligands are important. Catecholamine (dopamine, epinephrine, and norepinephrine) are able to form Fe(III) complexes whose extension in the coordination number depends upon the pH. Fe(III)-catecholamine complexes have been related with the development of several pathologies. In this work, the ability of catecholamines to enhance the oxidative degradation of an organic substrate (veratryl alcohol, VA) through Fenton and Fenton-like reactions was studied. The initial VA degradation rate at different pH values and its relationship to the different iron species present in solution were determined. Furthermore, the oxidative degradation of VA after 24 hours of reaction and its main oxidation products were also determined. The catecholamine-driven Fenton and Fenton-like systems showed higher VA degradation compared to unmodified Fenton or Fenton-like systems, which also showed an increase in the oxidation state of the VA degradation product. All of this oxidative degradation takes place at pH values lower than 5.50, where the primarily responsible species would be the Fe(III) mono-complex. The presence of Fe(III) mono-complex is essential in the ability of catecholamines to increase the oxidative capacity of Fenton systems.

Mechanism of postarrhythmic renal vasoconstriction in the anesthetized dog.

PubMed

Katholi, R E; Oparil, S; Urthaler, F; James, T N

1979-07-01

The mechanism of postarrhythmic renal vasoconstriction was studied in 28 dogs anesthetized with pentobarbital sodium (30 mg/kg i.v.). Rapid atrial or ventricular pacing or induction of atrial fibrilation were used to produce at least 20% prompt decrease in cardiac output and mean arterial blood pressure. Return to control cardiac output and blood pressure occurred within 3 minutes after cessation of the arrhythmia, but renal blood flow remained significantly decreased (26%) with gradual recovery by 17.7 +/- 6.6 min. Infusion of phentolamine (0.25 mg/min) into the renal artery, intravenous hexamethonium (l mg/kg), adrenal demedullation, or cooling the cervical vagi prevented postarrhythmic renal vasoconstriction. In contrast, renal denervation, intravenous bretylium (10 mg/kg), intravenous atropine (0.5 mg/kg) or intrarenal SQ 20881 (0.20 mg/min) has no effect on postarrhythmic renal vasoconstriction. Intravenous propranolol (0.5 mg/kg) intensified postarrhythmic renal vasoconstriction. These data suggested that the postarrhythmic renal vasoconstrictive response required intact vagi and was due to alpha adrenergic stimulation by adrenal catecholamines. However, femoral arterial catecholamine levels were not elevated above control during postarrhythmic renal vasoconstriction. We therefore sought local vascular pathways by which catecholamines might reach the kidneys. An adrenorenal vascular network was found in each dog. Collection of catecholamines from these vessels during postarrhythmic renal vasoconstriction in six dogs revealed catecholamine concentrations threefold higher than simultaneously collected femoral arterial catecholamines levels. Because ligation of these vessels abolished postarrhythmic renal vasoconstriction in each dog, we conclude that postarrhythmic renal vasconstriction is due to adrenal catecholamines reaching the kidneys through an adreno-renal vascular network and that the response requires intact vagi.

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.

PubMed

Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan

2014-12-01

Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of "autotoxicity"-inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the "catecholaldehyde hypothesis" for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. Published by Elsevier Inc.

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders☆

PubMed Central

Goldstein, David S.; Kopin, Irwin J.; Sharabi, Yehonatan

2015-01-01

Several neurodegenerative diseases involve loss of catecholamine neurons—Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of “autotoxicity”—inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the “catecholaldehyde hypothesis” for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. PMID:24945828

[Studies on the relationship between beta-adrenergic receptor density on cell wall lymphocytes, total serum catecholamine level and heart rate in patients with hyperthyroidism].

PubMed

Gajek, J; Zieba, I; Zyśko, D

2000-08-01

Hyperthyreosis mimics the hyperadrenergic state and its symptoms were though to be dependent on increased level of catecholamines. Another reason for the symptoms could be the increased density or affinity of beta-adrenergic receptors to catecholamines. The aim of the study was to examine the elements of sympathetic nervous system, thyroid hormones level and their influence on heart rate control in patients with hyperthyreosis. The study was carried out in 18 women, mean age 48.9 +/- 8.7 yrs and 6 men, mean age 54.2 +/- 8.7 yrs. The control group consisted of 30 healthy persons matched for age and sex. We examined the density of beta-adrenergic receptors using radioligand labelling method with 125I-cyanopindolol, serum total catecholamines level with radioenzymatic assay kit, the levels of free thyroid hormones using radioimmunoassays and thyreotropine level with immunoradiometric assay. Maximal, minimal and mean heart rate were studied using Holter monitoring system. The density of beta-adrenergic receptors in hyperthyreosis was 37.3 +/- 21.7 vs 37.2 +/- 18.1 fmol/mg in the control group (p = NS). Total catecholamines level was significantly decreased in hyperthyreosis group: 1.5 +/- 0.89 vs 1.9 +/- 0.73 pmol/ml (p < 0.05). There was significantly higher minimal, maximal and mean heart rate in hyperthyreosis group (p < 0.0001, p < 0.0001 and p < 0.05 respectively). There was a weak inverse correlation between minimum heart rate and triiodothyronine level (r = -0.38, p < 0.05). An inverse correlation between triiodothyronine and catecholamines level (r = -0.49, p < 0.05) was observed. Beta-adrenergic receptors density is unchanged and catecholamines level is decreased in hyperthyreosis when compared to normal subjects. There is no correlation between minimal heart rate and adrenergic receptors density or catecholamines level in hyperthyreosis.

Norepinephrine and dopamine increase motility, biofilm formation, and virulence of Vibrio harveyi

PubMed Central

Yang, Qian; Anh, Nguyen D. Q.; Bossier, Peter; Defoirdt, Tom

2014-01-01

Vibrio harveyi is one of the major pathogens of aquatic organisms, affecting both vertebrates and invertebrates, and causes important losses in the aquaculture industry. In order to develop novel methods to control disease caused by this pathogen, we need to obtain a better understanding of pathogenicity mechanisms. Sensing of catecholamines increases both growth and production of virulence-related factors in pathogens of terrestrial animals and humans. However, at this moment, knowledge on the impact of catecholamines on the virulence of pathogens of aquatic organisms is lacking. In the present study, we report that in V. harveyi, norepinephrine (NE) and dopamine (Dopa) increased growth in serum-supplemented medium, siderophore production, swimming motility, and expression of genes involved in flagellar motility, biofilm formation, and exopolysaccharide production. Consistent with this, pretreatment of V. harveyi with catecholamines prior to inoculation into the rearing water resulted in significantly decreased survival of gnotobiotic brine shrimp larvae, when compared to larvae challenged with untreated V. harveyi. Further, NE-induced effects could be neutralized by α-adrenergic antagonists or by the bacterial catecholamine receptor antagonist LED209, but not by β-adrenergic or dopaminergic antagonists. Dopa-induced effects could be neutralized by dopaminergic antagonists or LED209, but not by adrenergic antagonists. Together, our results indicate that catecholamine sensing increases the success of transmission of V. harveyi and that interfering with catecholamine sensing might be an interesting strategy to control vibriosis in aquaculture. We hypothesize that upon tissue and/or hemocyte damage during infection, pathogens come into contact with elevated catecholamine levels, and that this stimulates the expression of virulence factors that are required to colonize a new host. PMID:25414697

Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

PubMed

Limesand, Sean W; Rozance, Paul J

2017-08-01

Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Accumulation of radioactivity after repeated infusion of 3H-adrenaline and 3H-noradrenaline in the rat as a model animal.

PubMed

Lepschy, M; Filip, T; Palme, R G

2014-10-01

Besides enzymatic inactivation, catecholamines bind non-enzymatically and irreversible to proteins. The physiological impact of these catecholamine adducts is still unclear. We therefore collected basic data about the distribution of catecholamine adducts in the rat after repeated intravenous administration of (3)H-adrenaline and (3)H-noradrenaline. In all animals radioactivity in blood increased until the last injection on Day 7 and decreased then slowly close to background values (plasma) or remained higher (erythrocytes). In all sampled tissues radioactivity could be found, but only in hair high amounts remained present even after 3 weeks. Half-life of rat serum albumin loaded with (3)H-adrenaline or (3)H-noradrenaline was not altered. This study provides basic knowledge about the distribution of catecholamines or their adducts, but physiological effects could not be demonstrated. However, for the first time deposition and accumulation of catecholamines (adducts) in the hair could be proven, suggesting that hair might be used for evaluating long term stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

Potentiometric and NMR complexation studies of phenylboronic acid PBA and its aminophosphonate analog with selected catecholamines

NASA Astrophysics Data System (ADS)

Ptak, Tomasz; Młynarz, Piotr; Dobosz, Agnieszka; Rydzewska, Agata; Prokopowicz, Monika

2013-05-01

Boronic acids are a class of intensively explored compounds, which according to their specific properties have been intensively explored in last decades. Among them phenylboronic acids and their derivatives are most frequently examined as receptors for diverse carbohydrates. In turn, there is a large gap in basic research concerning complexation of catecholamines by these compounds. Therefore, we decided to undertake studies on interaction of chosen catecholamines, namely: noradrenaline (norephinephrine), dopamine, L-DOPA, DOPA-P (phosphonic analog of L-DOPA) and catechol, with simple phenyl boronic acid PBA by means of potentiometry and NMR spectroscopy. For comparison, the binding properties of recently synthesized phenylboronic receptor 1 bearing aminophosphonate function in meta-position were investigated and showed promising ability to bind catecholamines. The protonation and stability constants of PBA and receptor 1 complexes were examined by potentiometry. The obtained results demonstrated that PBA binds the catecholamines with the following affinity order: noradrenaline ⩾ dopamine ≈ L-DOPA > catechol > DOPA-P, while its modified analog 1 reveals slightly different preferences: dopamine > noradrenaline > catechol > L-DOPA > DOPA-P.

Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

PubMed

Trump, D L; Livingston, J N; Baylin, S B

1977-10-01

A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

PubMed Central

Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

2008-01-01

Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

Synergic effect studies of the bi-enzymatic system laccase-peroxidase in a voltammetric biosensor for catecholamines.

PubMed

Leite, Oldair D; Lupetti, Karina O; Fatibello-Filho, Orlando; Vieira, Iolanda C; Barbosa, Aneli de M

2003-04-10

Several bi-enzymatic carbon paste biosensors modified with enzymes laccase from Pleurotus ostreatus fungi and peroxidase from zucchini (Cucurbita pepo) were constructed for evaluating the synergic effect of the two enzymes on the voltammetric biosensor response for various catecholamines. Initially was investigated the effect of pH from 5.0 to 7.5, temperature from 25 to 50 degrees C, initial stirring time from 30 to 150 s, scan rate from 10 to 60 mVs(-1) and potential pulse amplitude from 10 to 60 mV on the biosensor response for several catecholamines such as dopamine, adrenaline, isoprenaline and l-dopa. It was observed a biosensor signal increase employing both enzymes, indicating thus there is a synergic effect between laccase and peroxidase, verified also in spectrophotometric studies, in the determination of these catecholamines.

The effect of morphine on the biosynthesis of catecholamines in the rat brain.

PubMed

Malini, M; Kwan, T K; Perumal, R

1994-02-01

In vivo studies involved monitoring the effect of morphine administration on catecholamine biosynthesis by the brain while in vitro studies involved studying the effect of morphine on the uptake of tritiated tyrosine by synaptosomes and its subsequent incorporation into the catecholamines. The extremely low levels of these endogenous compounds required the use of High Performance Liquid Chromatography with electrochemical detection. Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content. At a dosage of 60 mg/kg, dopamine levels were elevated while noradrenaline was depleted. Morphine, at a concentration of 1 x 10(-5)M increases the incorporation of tritiated tyrosine into dopamine and dihydroxy phenylacetic acid in synaptosomal preparations.

Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

PubMed

Guezennec, C Y; Defer, G; Cazorla, G; Sabathier, C; Lhoste, F

1986-01-01

The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

PubMed

Jepma, Marieke; Murphy, Peter R; Nassar, Matthew R; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

2016-10-01

Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Horishita, Takafumi; Toyohira, Yumiko; Shao, Hui; Bai, Jie; Bo, Haixia; Song, Xinbo; Ishikane, Shin; Yoshinaga, Yukari; Satoh, Noriaki; Tsutsui, Masato; Yanagihara, Nobuyuki

2017-04-01

Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003-0.005%) and SJ-2 (0.3-100 μM) also inhibited 45 Ca 2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14 C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003-0.001%) and SJ-2 (1-100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Catecholamine-Induced β2-adrenergic receptor activation mediates desensitization of gastric cancer cells to trastuzumab by upregulating MUC4 expression.

PubMed

Shi, Ming; Yang, Zhengyan; Hu, Meiru; Liu, Dan; Hu, Yabin; Qian, Lu; Zhang, Wei; Chen, Hongyu; Guo, Liang; Yu, Ming; Song, Lun; Ma, Yuanfang; Guo, Ning

2013-06-01

Trastuzumab is currently used for patients with Her2(+) advanced gastric cancer. However, the response rate to trastuzumab among the patients is low. The molecular mechanisms underlying trastuzumab resistance in gastric cancer are unknown. Our in vitro data show that activation of β2-adrenergic receptor (β2-AR) triggered by catecholamine caused "targeting failure" of trastuzumab in gastric cancer cells. The antitumor activities of trastuzumab were significantly impeded by chronic catecholamine stimulation in gastric cancer cells and in the mice bearing human gastric cancer xenografts. Mechanistically, catecholamine induced upregulation of the MUC4 expression at both transcription and protein levels via activating STAT3 and ERK. The effects of catecholamine could be effectively blocked by β2-AR antagonist ICI-118,551, indicating that β2-AR-mediated signaling pathway plays a key role in upregulation of MUC4, which was previously demonstrated to interfere with the recognition and physical binding of trastuzumab to Her2 molecules. Moreover, a significant elevation of the MUC4 level was observed in the xenograft tissues in nude mice chronically treated with isoproterenol. Knockdown of MUC4 restored the binding activities of trastuzumab to Her2-overexpressing gastric cancer cells. In addition, coexpression of β2-AR and MUC4 were observed in gastric cancer tissues. Our data indicated a novel trastuzumab resistance mechanism, by which catecholamine-induced β2-AR activation mediates desensitization of gastric cancer cells to trastuzumab through upregulating the MUC4 expression.

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment

PubMed Central

Jepma, Marieke; Nassar, Matthew R.; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

2016-01-01

Adaptive behavior in a changing world requires flexibly adapting one’s rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the ‘learning rate’). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG—an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex—predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables—capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief—on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants’ baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change. PMID:27792728

Tuning Selectivity of Fluorescent Carbon Nanotube-Based Neurotransmitter Sensors.

PubMed

Mann, Florian A; Herrmann, Niklas; Meyer, Daniel; Kruss, Sebastian

2017-06-28

Detection of neurotransmitters is an analytical challenge and essential to understand neuronal networks in the brain and associated diseases. However, most methods do not provide sufficient spatial, temporal, or chemical resolution. Near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) have been used as building blocks for sensors/probes that detect catecholamine neurotransmitters, including dopamine. This approach provides a high spatial and temporal resolution, but it is not understood if these sensors are able to distinguish dopamine from similar catecholamine neurotransmitters, such as epinephrine or norepinephrine. In this work, the organic phase (DNA sequence) around SWCNTs was varied to create sensors with different selectivity and sensitivity for catecholamine neurotransmitters. Most DNA-functionalized SWCNTs responded to catecholamine neurotransmitters, but both dissociation constants ( K d ) and limits of detection were highly dependent on functionalization (sequence). K d values span a range of 2.3 nM (SWCNT-(GC) 15 + norepinephrine) to 9.4 μM (SWCNT-(AT) 15 + dopamine) and limits of detection are mostly in the single-digit nM regime. Additionally, sensors of different SWCNT chirality show different fluorescence increases. Moreover, certain sensors (e.g., SWCNT-(GT) 10 ) distinguish between different catecholamines, such as dopamine and norepinephrine at low concentrations (50 nM). These results show that SWCNTs functionalized with certain DNA sequences are able to discriminate between catecholamine neurotransmitters or to detect them in the presence of interfering substances of similar structure. Such sensors will be useful to measure and study neurotransmitter signaling in complex biological settings.

Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts

PubMed Central

Jeong, Kyuho; Kwon, Hayeong; Min, Chanhee

2009-01-01

We investigated the effect of phenylephrine (PE)- and isoproterenol (ISO)-induced cardiac hypertrophy on subcellular localization and expression of caveolin-3 and STAT3 in H9c2 cardiomyoblast cells. Caveolin-3 localization to plasma membrane was attenuated and localization of caveolin-3 to caveolae in the plasma membrane was 24.3% reduced by the catecholamine-induced hypertrophy. STAT3 and phospho-STAT3 were up-regulated but verapamil and cyclosporin A synergistically decreased the STAT3 and phospho-STAT3 levels in PE- and ISO-induced hypertrophic cells. Both expression and activation of STAT3 were increased in the nucleus by the hypertrophy. Immunofluorescence analysis revealed that the catecholamine-induced hypertrophy promoted nuclear localization of pY705-STAT3. Of interest, phosphorylation of pS727-STAT3 in mitochondria was significantly reduced by catecholamine-induced hypertrophy. In addition, mitochondrial complexes II and III were greatly down-regulated in the hypertrophic cells. Our data suggest that the alterations in nuclear and mitochondrial activation of STAT3 and caveolae localization of caveolin-3 are related to the development of the catecholamine-induced cardiac hypertrophy. PMID:19299911

Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

PubMed

Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

2014-03-01

Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Catecholamine crisis during induction of general anesthesia : A case report.

PubMed

Sonntagbauer, M; Koch, A; Strouhal, U; Zacharowski, K; Weber, C F

2018-03-01

Catecholamine crises associated with pheochromocytoma may cause life-threatening cardiovascular conditions. We report the case of a 75-year-old male who developed a hypertensive crisis during induction of general anesthesia for elective resection of a cervical neuroma due to an undiagnosed pheochromocytoma. Hemodynamic instability occurred immediately after the injection of fentanyl, propofol and rocuronium, prior to laryngoscopy and in the absence of any manipulation of the abdomen. In this case report, we present the management of this incident and discuss the underlying pathophysiology triggering a catecholamine crisis.

Night-rest urinary catecholamine excretion in relation to aspects of free time, work and background data in a teacher group.

PubMed

Kinnunen, U; Vihko, V

1991-01-01

Free time, work and background data were related to night-rest catecholamine excretion rates in a teacher group (n = 137) during an autumn term. The explained interindividual variance increased slightly towards the end of the term. Adrenaline excretion was predicted better than noradrenaline, notedly by coffee consumption, amount of physical activity, and subjective stress feelings which explained 16% of the variance in adrenaline excretion during night rest. However, the results indicated that the differences in catecholamine excretion during night rest remained mostly unpredictable.

Rapid changes in synaptic vesicle cytochemistry after depolarization of cultured cholinergic sympathetic neurons

PubMed Central

1985-01-01

Sympathetic neurons taken from rat superior cervical ganglia and grown in culture acquire cholinergic function under certain conditions. These cholinergic sympathetic neurons, however, retain a number of adrenergic properties, including the enzymes involved in the synthesis of norepinephrine (NE) and the storage of measurable amounts of NE. These neurons also retain a high affinity uptake system for NE; despite this, the majority of the synaptic vesicles remain clear even after incubation in catecholamines. The present study shows, however, that if these neurons are depolarized before incubation in catecholamine, the synaptic vesicles acquire dense cores indicative of amine storage. These manipulations are successful when cholinergic function is induced with either a medium that contains human placental serum and embryo extract or with heart-conditioned medium, and when the catecholamine is either NE or 5-hydroxydopamine. In some experiments, neurons are grown at low densities and shown to have cholinergic function by electrophysiological criteria. After incubation in NE, only 6% of the synaptic vesicles have dense cores. In contrast, similar neurons depolarized (80 mM K+) before incubation in catecholamine contain 82% dense-cored vesicles. These results are confirmed in network cultures where the percentage of dense-cored vesicles is increased 2.5 to 6.5 times by depolarizing the neurons before incubation with catecholamine. In both single neurons and in network cultures, the vesicle reloading is inhibited by reducing vesicle release during depolarization with an increased Mg++/Ca++ ratio or by blocking NE uptake either at the plasma membrane (desipramine) or at the vesicle membrane (reserpine). In addition, choline appears to play a competitive role because its presence during incubation in NE or after reloading results in decreased numbers of dense-cored vesicles. We conclude that the depolarization step preceding catecholamine incubation acts to empty the vesicles of acetylcholine, thus allowing them to reload with catecholamine. These data also suggest that the same vesicles may contain both neurotransmitters simultaneously. PMID:4008529

Biochemical diagnosis of phaeochromocytoma: two instructive case reports.

PubMed Central

Stewart, M F; Reed, P; Weinkove, C; Moriarty, K J; Ralston, A J

1993-01-01

The biochemical features of two patients with phaeochromocytomas illustrate the inadvisability of depending on a single group of analytes for the diagnosis. The first case presented as a surgical emergency with retroperitoneal haemorrhage. Biochemical diagnosis was difficult since total 24 hour urinary free catecholamine excretion was within normal limits in two out of three samples, and only marginally raised in the third with an atypical preponderance of adrenaline. Plasma catecholamine concentrations were also normal. But urinary excretion of the catecholamine metabolites, metadrenaline and 4-hydroxy-3-methoxy mandelic acid (HMMA), was consistently raised. In contrast, the second patient presenting with headache and labile hypertension showed normal metabolite excretion in the face of grossly increased free noradrenaline excretion and raised plasma noradrenaline concentrations. It is therefore recommend that, as well as urinary free catecholamines, one group of their main metabolites, the 3-methoxy amines (normetadrenaline and metadrenaline) or HMMA, should routinely be measured whenever a phaeochromocytoma is suspected. PMID:8463426

[Urinary excretion of catecholamines in obese subjects and in diabetics (author's transl)].

PubMed

Giorgino, R; Nardelli, G M; Scardapane, R

1976-03-01

95 obese subjects, 40 diabetics and 22 normal controls were investigated. The weight of all obese subjects was at least 20% higher than the ideal weight. Catecholamine excretion was determined a few days after hospitalization to minimize the influence of environmental changes. Spectrofluorimetric estimation of adrenaline and noradrenaline in the urine was carried out according to the method of von Euler and Lihajko. Statistical analysis of the results showed a significant increase in both adrenaline and noradrenaline excretion in the group of obeses subjects compared with the diabetics. The increased catecholamine excretion may represent the response of the adrenal medulla to the stress of the disease. Such an increase may be responsible for perpheral insulin resistence and hence acts as a diabetogenic factor. The results obtained emphasize the influence of catecholamines on insulin responsiveness, possibly constituting a major contribution to the diabetic state.

Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.

PubMed

Gallo, Valentina P; Accordi, Fiorenza; Chimenti, Claudio; Civinini, Annalena; Crivellato, Enrico

2016-01-01

In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla. Copyright © 2016 Elsevier Inc. All rights reserved.

[Significance of 3-methoxytyramine urine measurement in the diagnosis of pheochromocytomas and paragangliomas: about 28 patients].

PubMed

Le Jacques, Aurélien; Abalain, Jean-Hervé; Le Saos, Fabienne; Carré, Jean-Luc

2011-01-01

Measurement of catecholamines derivatives is used to diagnose tumors such as pheochromocytomas and paragangliomas. Despite the low incidence of these diseases, their diagnosis is essential because of potentially lethal episodes of malignant hypertension related to an inappropriate secretion of catecholamines by these tumors. The catecholamines derivatives include 3-methoxytyramine, normetanephrine and metanephrine, assayed in urine or plasma. The significance of the measurement of urinary 3-methoxytyramine was addressed by analysing the records of 28 patients aged 25 to 84 years with isolated elevation of this derivative, with non-pathological urinary rates of metanephrine and normetanephrine, that might help suspect a catecholamine inappropriate secretion. In these situations, no pheochromocytoma or paraganglioma was diagnosed. This study, after discussing possible biases in the clinical care and diagnosis approach of these patients, raises the question of the relevance of this assay in the diagnostic management of these diseases.

DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis

PubMed Central

Piston, Dominik; Alvarez-Erviti, Lydia; Bansal, Vikas; Gargano, Daniela; Yao, Zhi; Szabadkai, Gyorgy; Odell, Mark; Puno, M Rhyan; Björkblom, Benny; Maple-Grødem, Jodi; Breuer, Peter; Kaut, Oliver; Larsen, Jan Petter; Bonn, Stefan; Møller, Simon Geir; Wüllner, Ullrich; Schapira, Anthony H V

2017-01-01

Abstract DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson’s disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease. PMID:29016861

Catecholaminergic systems in stress: structural and molecular genetic approaches.

PubMed

Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

2009-04-01

Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.

GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

PubMed Central

Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

2016-01-01

Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal regulation of epinephrine synthesis during stress. PMID:19503019

Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

PubMed

Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

2017-07-01

Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A Potential Benefit of Albinism in Astyanax Cavefish: Downregulation of the oca2 Gene Increases Tyrosine and Catecholamine Levels as an Alternative to Melanin Synthesis

PubMed Central

Parkhurst, Amy; Jeffery, William R.

2013-01-01

Albinism, the loss of melanin pigmentation, has evolved in a diverse variety of cave animals but the responsible evolutionary mechanisms are unknown. In Astyanax mexicanus, which has a pigmented surface dwelling form (surface fish) and several albino cave-dwelling forms (cavefish), albinism is caused by loss of function mutations in the oca2 gene, which operates during the first step of the melanin synthesis pathway. In addition to albinism, cavefish have evolved differences in behavior, including feeding and sleep, which are under the control of the catecholamine system. The catecholamine and melanin synthesis pathways diverge after beginning with the same substrate, L-tyrosine. Here we describe a novel relationship between the catecholamine and melanin synthesis pathways in Astyanax. Our results show significant increases in L-tyrosine, dopamine, and norepinephrine in pre-feeding larvae and adult brains of Pachón cavefish relative to surface fish. In addition, norepinephrine is elevated in cavefish adult kidneys, which contain the teleost homologs of catecholamine synthesizing adrenal cells. We further show that the oca2 gene is expressed during surface fish development but is downregulated in cavefish embryos. A key finding is that knockdown of oca2 expression in surface fish embryos delays the development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine. We conclude that a potential evolutionary benefit of albinism in Astyanax cavefish may be to provide surplus L-tyrosine as a precursor for the elevated catecholamine synthesis pathway, which could be important for adaptation to the challenging cave environment. PMID:24282555

Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients.

PubMed

Verly, Iedan R N; van Kuilenburg, André B P; Abeling, Nico G G M; Goorden, Susan M I; Fiocco, Marta; Vaz, Frédéric M; van Noesel, Max M; Zwaan, C Michel; Kaspers, GertJan L; Merks, Johannes H M; Caron, Huib N; Tytgat, Godelieve A M

2017-02-01

Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamin and myosin regulate differential exocytosis from mouse adrenal chromaffin cells.

PubMed

Chan, Shyue-An; Doreian, Bryan; Smith, Corey

2010-11-01

Neuroendocrine chromaffin cells of the adrenal medulla represent a primary output for the sympathetic nervous system. Chromaffin cells release catecholamine as well as vaso- and neuro-active peptide transmitters into the circulation through exocytic fusion of large dense-core secretory granules. Under basal sympathetic activity, chromaffin cells selectively release modest levels of catecholamines, helping to set the "rest and digest" status of energy storage. Under stress activation, elevated sympathetic firing leads to increased catecholamine as well as peptide transmitter release to set the "fight or flight" status of energy expenditure. While the mechanism for catecholamine release has been widely investigated, relatively little is known of how peptide transmitter release is regulated to occur selectively under elevated stimulation. Recent studies have shown selective catecholamine release under basal stimulation is accomplished through a transient, restricted exocytic fusion pore between granule and plasma membrane, releasing a soluble fraction of the small, diffusible molecules. Elevated cell firing leads to the active dilation of the fusion pore, leading to the release of both catecholamine and the less diffusible peptide transmitters. Here we propose a molecular mechanism regulating the activity-dependent dilation of the fusion pore. We review the immediate literature and provide new data to formulate a working mechanistic hypothesis whereby calcium-mediated dephosphorylation of dynamin I at Ser-774 leads to the recruitment of the molecular motor myosin II to actively dilate the fusion pore to facilitate release of peptide transmitters. Thus, activity-dependent dephosphorylation of dynamin is hypothesized to represent a key molecular step in the sympatho-adrenal stress response.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

PubMed

Ohara, Nobumasa; Uemura, Yasuyuki; Mezaki, Naomi; Kimura, Keita; Kaneko, Masanori; Kuwano, Hirohiko; Ebe, Katsuya; Fujita, Toshio; Komeyama, Takeshi; Usuda, Hiroyuki; Yamazaki, Yuto; Maekawa, Takashi; Sasano, Hironobu; Kaneko, Kenzo; Kamoi, Kyuzi

2016-10-12

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

Perioperative Management of Severe Hypertension during Laparoscopic Surgery for Pheochromocytoma

PubMed Central

Erdoğan, Mehmet Ali; Uçar, Muharrem; Özkan, Ahmet Selim; Özgül, Ülkü; Durmuş, Mahmut

2016-01-01

Phaeochromocytoma is a catecholamine-secreting vascular tumour that is derived from chromaffin cell. Lethal cardiovascular complications, such as serious hypertension, myocardial infarction and aortic dissection, may occur because of uncontrolled catecholamine release. Each stage of anaesthesia management has vital importance because of this destructive catecholamine secretion that may occur during induction, perioperative stage and surgical manipulation. In this study, we report regarding the preoperative preparation and severe, persistent hypertension attack management with a combination of α-adrenergic blockade, β-adrenergic blockade, sodium nitroprusside and remifentanil in a patient who underwent laparoscopic surgery for phaeochromocytoma. PMID:27366556

The choice of catecholamines in septic shock: more and more good arguments to strengthen the known position, but don't lose the faith!

PubMed

Meier-Hellmann, Andreas

2006-01-01

The choice of catecholamines for hemodynamic stabilisation in septic shock patients has been an ongoing debate for several years. Several studies have investigated the regional effects in septic patients. Because of an often very small sample size, because of inconsistent results and because of methodical problems in the monitoring techniques used in these studies, however, it is not possible to provide clear recommendations concerning the use of catecholamines in sepsis. Prospective and adequate-sized studies are necessary because outcome data are completely lacking.

Determination of catecholamine in human serum by a fluorescent quenching method based on a water-soluble fluorescent conjugated polymer-enzyme hybrid system.

PubMed

Huang, Hui; Gao, Yuan; Shi, Fanping; Wang, Guannan; Shah, Syed Mazhar; Su, Xingguang

2012-03-21

In this paper, a sensitive water-soluble fluorescent conjugated polymer biosensor for catecholamine (dopamine DA, adrenaline AD and norepinephrine NE) was developed. In the presence of horse radish peroxidase (HRP) and H(2)O(2), catecholamine could be oxidized and the oxidation product of catecholamine could quench the photoluminescence (PL) intensity of poly(2,5-bis(3-sulfonatopropoxy)-1,4-phenylethynylenealt-1,4-poly(phenylene ethynylene)) (PPESO(3)). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of DA, AD and NE in the concentration ranges of 5.0 × 10(-7) to 1.4 × 10(-4), 5.0 × 10(-6) to 5.0 × 10(-4), and 5.0 × 10(-6) to 5.0 × 10(-4) mol L(-1), respectively. The detection limit for DA, AD and NE was 1.4 × 10(-7) mol L(-1), 1.0 × 10(-6) and 1.0 × 10(-6) mol L(-1), respectively. The PPESO(3)-enzyme hybrid system based on the fluorescence quenching method was successfully applied for the determination of catecholamine in human serum samples with good accuracy and satisfactory recovery. The results were in good agreement with those provided by the HPLC-MS method.

β2-AR activation induces chemoresistance by modulating p53 acetylation through upregulating Sirt1 in cervical cancer cells.

PubMed

Chen, Hongyu; Zhang, Wei; Cheng, Xiang; Guo, Liang; Xie, Shuai; Ma, Yuanfang; Guo, Ning; Shi, Ming

2017-07-01

It has been suggested that β2-adrenergic receptor (β2-AR)-mediated signaling induced by catecholamines regulates the degradation of p53. However, the underlying molecular mechanisms were not known. In the present study, we demonstrated that catecholamines upregulated the expression of silent information regulator 1 (Sirt1) through activating β2-AR-mediated signaling pathway, since selective β2-AR antagonist ICI 118, 551 and non-selective β-blocker proprenolol effectively repressed isoproterenol (ISO)-induced Sirt1 expression. Catecholamines inhibited doxorubicin (DOX)-induced p53 acetylation and transcription-activation activities by inducing the expression of Sirt1. Knockdown of the Sirt1 expression by the specific siRNA remarkably blocked the inhibitory effects of ISO on DOX-induced p53 acetylation. In addition, we demonstrated that catecholamines induced resistance of cervical cancer cells to chemotherapeutics both in vitro and in vivo and that β2-AR was overexpressed in cervical cancer tissues. Our data suggest that the p53-dependent, chemotherapeutics-induced cytotoxicity in cervical cancer cells may be compromised by catecholamines-induced upregulation of the Sirt1 expression through activating the β2-AR signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

DISTRIBUTION OF ATRAZINE IN PC12 CELLS AND MODULATION OF CATECHOLAMINE SYNTHESIS

EPA Science Inventory

Previously, we reported that atrazine disrupts ovarian function by altering hypothalamic catecholamine (CA) concentrations and the consequent regulation of pituitary LH release and prolactin secretion in the young female rat. We also showed that atrazine directly interacts with t...

Excessive Catecholamine Secretion and the Activation of the Renin-Angiotensin-Aldosterone-System in Patients with Pheochromocytoma: A Single Center Experience and Overview of the Literature.

PubMed

Haase, Matthias; Dringenberg, Till; Allelein, Stephanie; Willenberg, Holger S; Schott, Matthias

2017-10-01

Catecholamines stimulate renin-secretion in the juxtaglomerular cells of the kidney and a number of case reports suggest an association between pheochromocytoma and activation of the RAAS. Therefore, it could be asked whether patients suffering from pheochromocytoma with high concentrations of circulating catecholamines present with oversecretion of renin and aldosterone. We identified twelve patients with excessive catecholamine secretion due to pheochromocytoma and compared them to a group of twelve patients with essential hypertension (EH) with regard to the activation of the renin-angiotensin-aldosterone-system (RAAS). The PubMed database was screened for studies that investigate the association between pheochromocytoma and activation of the RAAS. The plasma concentrations of metanephrines (19.9-fold) and normetanephrines (29.5-fold) were significantly higher in the pheochromocytoma group than in the EH group. Renin and aldosterone levels were 1.3-fold and 1.6-fold higher, respectively, as compared to the EH group, whereas the differences were not statistically significant. There was no significant correlation between plasma metanephrine or normetanephrine levels and the plasma renin concentration (r s =0.077, r s =0.049, respectively) in our patients. The data from our institution and from review of literature suggest that an association between pheochromocytoma in the context of high plasma catecholamine levels and activation of the RAAS is present. However, results have not been consistent. Thus, other causes of RAAS-activation should be considered also in the presence of pheochromocytoma or reinvestigation for aldosteronism should be offered to such patients after removal of the catecholamine-producing tumour. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats.

PubMed

Dronjak, S; Gavrilovic, L

2006-06-01

Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4 degrees C, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(3H-methyl)-methionine was used. The O-methylated derivatives were oxidized to 3H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat.

PubMed

Tanaka, Kenjiro; Shimizu, Takahiro; Yanagita, Toshihiko; Nemoto, Takayuki; Nakamura, Kumiko; Taniuchi, Keisuke; Dimitriadis, Fotios; Yokotani, Kunihiko; Saito, Motoaki

2014-01-01

Haemopressin and RVD-haemopressin, derived from the haemoglobin α-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin-derived peptides on this bombesin-induced response Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin α-positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN, a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. Bombesin given i.c.v. dose-dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine-induced secretion of catecholamines from chromaffin cells. The bombesin-induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin α-positive spinally projecting neurons in the PVN. The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow. © 2013 The British Pharmacological Society.

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

PubMed

Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

[Effect of gamma-aminobutyric acid on peripheral mechanisms regulating autonomic functions].

PubMed

Godovalova, L A

1976-01-01

Experiments with cats ascertained the potentiating action of GABA (100,300,500 mg/kg) on the pressor reactions of the small intestine vessels, the systemic arterial pressure, depressing (100 mg/kg) and facilitating (500 mg/kg) effect upon the reactions of inhibition of the small intestine motor activity evoked by the efferent stimulation of the celiac nerve. Adrenolytics (dihydroergotoxin, inderal) abolished the facilitating effects of GABA. The latter (0.01 solution) inhibited spontaneous contractions of isolated small intestine lengths. As proved histochemically GABA (500 mg/kg) reduces the catecholamines content in the suprarenals, in the solar plexus ganglia and in vessles "in vivo". It also increases the catecholamines content in the small intestine wall in experiments in vivo and reduces in vitro tests. The potentiating action of GABA on the vegetative reactions in efferent stimulation of the ciliac nerve occurs, apparently, due to an increased ejection of catecholamines by suprarenals and lowered the content of catecholamines in the solar plexus ganglia, which causes facilitated conduction of excitation in the ganglia.

The apelinergic system as an alternative to catecholamines in low-output septic shock.

PubMed

Coquerel, David; Sainsily, Xavier; Dumont, Lauralyne; Sarret, Philippe; Marsault, Éric; Auger-Messier, Mannix; Lesur, Olivier

2018-01-19

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the "maintaining blood pressure" paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

A painful pulsatile abdominal mass in a young man with elevated blood pressures: an unusual presentation of phaeochromocytoma.

PubMed

Lee, B M K; Ti, L K

2002-08-01

We report an unusual presentation of phaeochromocytoma in a young man with a painful, pulsatile abdominal mass and elevated blood pressures. This led to a delay in diagnosis and resulted in the administration of triggers of catecholamine release, possibly causing a catecholamine surge. This caused the development of catecholamine-induced cardiomyopathy and multiple organ failure, requiring inotropic and ventilatory support, intra-aortic balloon pump and dialysis. Fortunately, his condition reversed with supportive treatment and alpha-adrenergic blockade. This illustrates the importance of having a high index of suspicion of phaeochromocytoma, especially in young patients with elevated blood pressures.

Phentolamine tests and catecholamine levels in normotensive CVA patients.

PubMed

Favazza, A R

1974-11-01

Ten normotensive patients diagnosed as having a CVA had Regitine tests and urinary VMA and catecholamine determinations during the first day of hospitalization. The VMA and catecholamine levels were all within normal limits (except for one elevated VMA level) but did not correlate well with each other. The average response to phentolamine was an average drop in blood pressure of 30mm. Hg systolic and 19 mm. Hg diastolic. Mechanisms by which hypertensive states or cerebral damage might effect blood pressure are discussed. It is suggested that CNS damage might induce a vasolabile or hypersensitive state via connections and consequent alterations in the autonomic vasomotor system.

Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

NASA Technical Reports Server (NTRS)

Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

1980-01-01

The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

Reduced catecholamine response to exercise in amenorrheic athletes

USDA-ARS?s Scientific Manuscript database

Studies have found an array of endocrine disturbances related to energy deprivation in women with functional hypothalamic amenorrhea. Purpose: We examined the catecholamine response to exercise in five eumenorrheic (EU) and five amenorrheic (AM) athletes, matched by age (mean T SEM: EU = 29.8 T 2.5 ...

21 CFR 862.1165 - Catecholamines (total) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1165 - Catecholamines (total) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1165 - Catecholamines (total) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1165 - Catecholamines (total) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

21 CFR 862.1165 - Catecholamines (total) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Catecholamines (total) test system. 862.1165 Section 862.1165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

ALTERATION OF CATECHOLAMINES IN PHOECHROMOCYTOMA (PC12) CELLS IN VITRO BY THE METABOLITES OF CHLOROTRIAZINE HERBICIDE

EPA Science Inventory

The effects of four major chlorotriazine metabolites on the constitutive synthesis of the catecholamines dopamine (DA) and norepinephrine (NE) were examined using undifferentiated PC12 cells. NE release and intracellular DA and NE concentrations were quantified following treatme...

Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms.

PubMed

Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Hasler, Gregor

2013-09-01

There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

A toxin fraction (FTX) from the funnel-web spider poison inhibits dihydropyridine-insensitive Ca2+ channels coupled to catecholamine release in bovine adrenal chromaffin cells.

PubMed

Duarte, C B; Rosario, L M; Sena, C M; Carvalho, A P

1993-03-01

In adrenal chromaffin cells, depolarization-evoked Ca2+ influx and catecholamine release are partially blocked by blockers of L-type voltage-sensitive Ca2+ channels. We have now evaluated the sensitivity of the dihydropyridine-resistant components of Ca2+ influx and catecholamine release to a toxin fraction (FTX) from the funnel-web spider poison, which is known to block P-type channels in mammalian neurons. FTX (1:4,000 dilution, with respect to the original fraction) inhibited K(+)-depolarization-induced Ca2+ influx by 50%, as monitored with fura-2, whereas nitrendipine (0.1-1 microM) and FTX (3:3), a synthetic FTX analogue (1 mM), blocked the [Ca2+]i transients by 35 and 30%, respectively. When tested together, FTX and nitrendipine reduced the [Ca2+]i transients by 70%. FTX or nitrendipine reduced adrenaline and noradrenaline release by approximately 80 and 70%, respectively, but both substances together abolished the K(+)-evoked catecholamine release, as measured by HPLC. The omega-conotoxin GVIA (0.5 microM) was without effect on K(+)-stimulated 45Ca2+ uptake. Our results indicate that FTX blocks dihydropyridine- and omega-conotoxin-insensitive Ca2+ channels that, together with L-type voltage-sensitive Ca2+ channels, are coupled to catecholamine release.

Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems.

PubMed

Goldstein, David S

2013-10-01

This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body's monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems-especially Parkinson disease-and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. Published 2013. Compr Physiol 3:1569-1610, 2013.

Diurnal Salivary Cortisol and Urinary Catecholamines Are Associated With Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Champaneri, Shivam; Xu, Xiaoqiang; Carnethon, Mercedes R.; Bertoni, Alain G.; Seeman, Teresa; Roux, Ana Diez; Golden, Sherita Hill

2011-01-01

Objective To examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status. Methods Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1,002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response (CAR), early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine. Results Participants with diabetes had significantly lower CAR (β=−0.19; 95% CI: −0.34 to −0.04) than those without diabetes in multivariable models. While men with diabetes had a non-significant trend toward lower total AUC (β=−1.56; 95% CI: −3.93 to 0.80), women with diabetes had significantly higher total AUC (β=2.62; 95% CI: 0.72 to 4.51) (p=0.02 for interaction) compared to those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines, compared to those without diabetes (p<0.05). Conclusions Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes. PMID:22209664

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

NASA Technical Reports Server (NTRS)

Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald

2005-01-01

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

Catecholamines and cognition after traumatic brain injury

PubMed Central

Jenkins, Peter O.; Mehta, Mitul A.

2016-01-01

Abstract Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems

PubMed Central

Goldstein, David S.

2016-01-01

This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body’s monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems—especially Parkinson disease—and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. PMID:24265239

Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning.

PubMed

Highland, Krista B; Costanzo, Michelle E; Jovanovic, Tanja; Norrholm, Seth D; Ndiongue, Rochelle B; Reinhardt, Brian J; Rothbaum, Barbara; Rizzo, Albert A; Roy, Michael J

2015-01-01

Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness.

Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis in the aged

PubMed Central

Camell, Christina D.; Sander, Jil; Spadaro, Olga; Lee, Aileen; Nguyen, Kim Y.; Wing, Allison; Goldberg, Emily L.; Youm, Yun-Hee; Brown, Chester W.; Elsworth, John; Rodeheffer, Matthew S.; Schultze, Joachim L.; Dixit, Vishwa Deep

2017-01-01

Catecholamine-induced lipolysis, the first step in generation of energy substrates through hydrolysis of triglycerides (TGs) 1, declines with age 2,3. The defect in mobilization of free fatty acids (FFA) in elderly is accompanied with increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation. While catecholamine signaling in adipocytes is normal in elderly, how lipolysis is impaired in aging remains unknown 2,4. Here we uncover that the adipose tissue macrophages (ATMs) regulate age-related reduction in adipocyte lipolysis by lowering the bioavailability of norepinephrine (NE). Unexpectedly, unbiased whole transcriptome analyses of adipose macrophages revealed that aging upregulates genes controlling catecholamine degradation in an NLRP3 inflammasome-dependent manner. Deletion of NLRP3 in aging restored catecholamine-induced lipolysis through downregulation of growth differentiation factor-3 (GDF3) and monoamine oxidase-a (MAOA) that is known to degrade NE. Consistent with this, deletion of GDF3 in inflammasome-activated macrophages improved lipolysis by decreasing MAOA and caspase-1. Furthermore, inhibition of MAOA reversed age-related reduction in adipose tissue NE concentration and restored lipolysis with increased levels of key lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Our study reveals that targeting neuro-innate signaling between sympathetic nervous system and macrophages may offer new approaches to mitigate chronic inflammation-induced metabolic impairment and functional decline. PMID:28953873

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arita, M.; Wada, A.; Takara, H.

In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. (/sup 3/H)Imipramine bound specifically to adrenal medullary cells. Binding was saturable,more » reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of (/sup 3/H)imipramine at the same concentrations as they inhibited /sup 22/Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of (/sup 3/H)imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.« less

DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

EPA Science Inventory

Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.

Das PC, McElroy WK, Cooper RL.

Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.

Epidemiological, wildlife, and lab...

Methylphenidate Improves Working Memory and Set-Shifting in AD/HD: Relationships to Baseline Memory Capacity

ERIC Educational Resources Information Center

Mehta, Mitul A.; Goodyer, Ian M.; Sahakian, Barbara J.

2004-01-01

Objective: Catecholamine stimulant drugs are highly efficacious treatments for attention deficit/hyperactivity disorders (AD/HD). Catecholamine modulation in humans influences performance of numerous cognitive tasks, including tests of attention and working memory (WM). Clear delineation of the effects of methylphenidate upon such cognitive…

POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

EPA Science Inventory

ABSTRACT

Potential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*
PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+
1Curriculum in Toxicology, University of North Carolina, Chape...

The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

PubMed

Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

2017-09-01

The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few reports are available on the anatomy and physiology of enteric dopamine neurons. Remarkably, this review limits the presence of enteric noradrenaline (and adrenaline) only within extrinsic sympathetic nerve terminals. This is based on careful morphological studies showing that the only catecholamine-containing neurons within ENS would be dopaminergic. This means that enteric pathology of catecholamine neurons should be conceived as axon pathology for noradrenaline neurons and whole cell pathology for dopamine neurons which would be the sole catecholamine cell within intrinsic circuitries affecting gut motility and secretions.The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network  controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudounipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine-containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as including Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few reports are available on the anatomy and physiology of enteric dopamine neurons. Remarkably, this review limits the presence of enteric noradrenaline (and adrenaline) only within extrinsic sympathetic nerve terminals. This is based on careful morphological studies showing that the only catecholamine-containing neurons within ENS would be dopaminergic. This means that enteric pathology of catecholamine neurons should be conceived as axon pathology for noradrenaline neurons and whole cell pathology for dopamine neurons which would be the sole catecholamine cell within intrinsic circuitries affecting gut motility and secretions.

Development of Sensitive and Direct Methods for Measuring Plasma Aldosterone and Catecholamine Concentrations

NASA Technical Reports Server (NTRS)

Haber, E.

1972-01-01

Radioimmunoassays for renin activity, angiotensin 1, and angiotensin 2 in the study of vasomotor regulation give new insight into the role of the renin system in maintaining postural homeostatsis. Similar laboratory procedures for specific assays of aldosterone and catecholamines achieve accurate determinations in small human blood samples.

Animal-Model Studies of Radiation-Induced Emesis and Its Control.

DTIC Science & Technology

1982-08-01

result of 6-OHDA was similar to that of haloperidol , one action of which is catecholamine receptor neuron blocking. The fact that 6- OHDA works strictly at...minutes preexposure n = 12 Delayed onset times Haloperidol Catecholamine Reduced number of S.2w, mg/kg i.m. blocker emetic episodes 45 :iinutes

The Control of Responsiveness in ADHD by Catecholamines: Evidence for Dopaminergic, Noradrenergic and Interactive Roles

ERIC Educational Resources Information Center

Oades, Robert D.; Sadile, Adolfo G.; Sagvolden, Terje; Viggiano, Davide; Zuddas, Alessandro; Devoto, Paola; Aase, Heidi; Johansen, Espen B.; Ruocco, Lucia A.; Russell, Vivienne A.

2005-01-01

We explore the neurobiological bases of attention deficit hyperactivity disorder (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems. The contributions of dopamine (DA) and noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD (e.g. hyperactivity, variable…

Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents.

PubMed

Merouze, P; Gaudemer, Y

1975-01-01

1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions.

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

PubMed Central

Wenisch, C; Parschalk, B; Weiss, A; Zedwitz-Liebenstein, K; Hahsler, B; Wenisch, H; Georgopoulos, A; Graninger, W

1996-01-01

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood. PMID:8807207

[Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma syndrome diagnosed during the past 20 years].

PubMed

Balog, Beatrice; Tőke, Judit; Róna, Kálmán; Szücs, Nikolette; Igaz, Péter; Pusztai, Péter; Sármán, Beatrix; Gláz, Edit; Kiss, Róbert; Patócs, Attila; Rácz, Károly; Tóth, Miklós

2015-04-19

Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells.

PubMed

Ges, Igor A; Brindley, Rebecca L; Currie, Kevin P M; Baudenbacher, Franz J

2013-12-07

Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped "cell traps", each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion/repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time.

Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naranjo, J.R.; Mocchetti, I.; Schwartz, J.P.

1986-03-01

In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone(1 ..mu..M) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 ..mu..M veratridine resulted in a depletion of enkephalin and catecholamine storesmore » after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 ..mu..M dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 ..mu..M) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated.« less

Photoaffinity labelling of MSH receptors on Anolis melanophores: effects of catecholamines, calcium and forskolin.

PubMed

Eberle, A N; Girard, J

1985-01-01

Photoaffinity labelling of MSH receptors on Anolis melanophores was used as a tool for studying the effects of catecholamines, calcium and forskolin on hormone-receptor interaction and receptor-adenylate cyclase coupling. Covalent attachment of photoreactive alpha-MSH to its receptor was suppressed in calcium-free buffer but was hardly influenced by catecholamines or forskolin. The longlasting signal generated by the covalent MSH-receptor complex was readily and reversibly abolished by adrenaline, noradrenaline, dopamine or clonidine or by the absence of calcium. The suppression of pigment dispersion by catecholamines was blocked by the simultaneous presence of yohimbine but not prazosin, indicating that the catecholamines antagonize the alpha-MSH signal by inhibitory action on the adenylate cyclase system through an alpha-2 receptor. Forskolin, which stimulates melanophores by direct action on the catalytic unit of the adenylate cyclase and at about the same speed as alpha-MSH, produced a slower and weaker response in the presence of noradrenaline. If MSH receptors were covalently labelled and then exposed to noradrenaline, the characteristics of the forskolin-induced response were identical to those of unlabelled cells that had not been exposed to noradrenaline. This may point to a partial restoration of receptor-adenylate cyclase coupling by forskolin. The results show that the longlasting stimulation of Anolis melanophores by photoaffinity labelling proceeds via a permanently stimulated adenylate-cyclase system whose coupling to the receptor depends on calcium and is abolished by alpha-2 receptor agonists. Calcium is also essential for hormone-receptor binding.

Role of catecholamines in maternal-fetal stress transfer in sheep.

PubMed

Rakers, Florian; Bischoff, Sabine; Schiffner, Rene; Haase, Michelle; Rupprecht, Sven; Kiehntopf, Michael; Kühn-Velten, W Nikolaus; Schubert, Harald; Witte, Otto W; Nijland, Mark J; Nathanielsz, Peter W; Schwab, Matthias

2015-11-01

We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones. Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent. Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes (P < .05). Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase (P < .05). Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in the presence of an unaltered oxygen supply. Adrenergic blockade prevented the stress-induced UBF decrease and, consequently, the fetal NE and blood pressure increase and the shift toward anaerobic metabolism. We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited. Copyright © 2015 Elsevier Inc. All rights reserved.

Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis

PubMed Central

Fischer, Katrin; Ruiz, Henry H.; Jhun, Kevin; Finan, Brian; Oberlin, Douglas J.; van der Heide, Verena; Kalinovich, Anastasia V.; Petrovic, Natasa; Wolf, Yochai; Clemmensen, Christoffer; Shin, Andrew C.; Divanovic, Senad; Brombacher, Frank; Glasmacher, Elke; Keipert, Susanne; Jastroch, Martin; Nagler, Joachim; Schramm, Karl-Werner; Medrikova, Dasa; Collden, Gustav; Woods, Stephen C.; Herzig, Stephan; Homann, Dirk; Jung, Steffen; Nedergaard, Jan; Cannon, Barbara; Tschöp, Matthias H.

2017-01-01

Adaptive thermogenesis is the process of heat generation in response to cold stimulation and is under the control of the sympathetic nervous system whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta3 adrenergic receptors to activate brown adipose tissue and by “browning” white adipose tissue. Recent studies reported that the alternative activation of macrophages in response to IL-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and to provide an alternative source of locally produced catecholamines during the thermogenic process. We here report that the deletion of Th in hematopoetic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with Interleukin-4 (IL-4), and conditioned media from IL-4 stimulated macrophages failed to induce expression of thermogenic genes, such as the one for uncoupling protein 1 (Ucp1) in adipocytes cultured with the conditioned media. Further, chronic IL-4 treatment failed to increase energy expenditure in WT, Ucp1-/- and Il4ra-/- mice. Consistent with these findings, adipose tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines and hence are not likely to play a direct role in adipocyte metabolism or adaptive thermogenesis. PMID:28414329

Magnetron sputtered diamond-like carbon microelectrodes for on-chip measurement of quantal catecholamine release from cells

PubMed Central

Gao, Yuanfang; Chen, Xiaohui; Gupta, Sanju; Gillis, Kevin D.; Gangopadhyay, Shubhra

2008-01-01

Carbon electrodes are widely used in electrochemistry due to their low cost, wide potential window, and low and stable background noise. Carbon-fiber electrodes (CFE) are commonly used to electrochemically measure “quantal” catecholamine release via exocytosis from individual cells, but it is difficult to integrate CFEs into lab-on-a-chip devices. Here we report the development of nitrogen doped diamond-like carbon (DLC:N) microelectrodes on a chip to monitor quantal release of catecholamines from cells. Advantages of DLC:N microelectrodes are that they are batch producible at low cost, and are harder and more durable than graphite films. The DLC:N microelectrodes were prepared by a magnetron sputtering process with nitrogen doping. The 30 μm by 40 μm DLC:N microelectrodes were patterned onto microscope glass slides by photolithography and lift-off technology. The properties of the DLC:N microelectrodes were characterized by AFM, Raman spectroscopy and cyclic voltammetry. Quantal catecholamine release was recorded amperometrically from bovine adrenal chromaffin cells on the DLC:N microelectrodes. Amperometric spikes due to quantal release of catecholamines were similar in amplitude and area as those recorded using CFEs and the background current and noise levels of microchip DLC:N electrodes were also comparable to CFEs. Therefore, DLC:N microelectrodes are suitable for microchip-based high-throughput measurement of quantal exocytosis with applications in basic research, drug discovery and cell-based biosensors. PMID:18493856

The Influence of Hyperthyroidism and Hypothyroidism on the β-Adrenergic Responsiveness of the Turkey Erythrocyte

PubMed Central

Bilezikian, John P.; Loeb, John N.; Gammon, Donald E.

1979-01-01

The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the β-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer β-adrenergic receptors than in normal cells as determined by the specific binding of [125I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of β-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the β-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects β-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both β-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, β-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP. PMID:219032

The novel iron chelator, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone, reduces catecholamine-mediated myocardial toxicity.

PubMed

Mladĕnka, Premysl; Kalinowski, Danuta S; Haskova, Pavlína; Bobrovová, Zuzana; Hrdina, Radomír; Simůnek, Tomás; Nachtigal, Petr; Semecký, Vladimĺr; Vávrová, Jaroslava; Holeckova, Magdaléna; Palicka, Vladimir; Mazurová, Yvona; Jansson, Patric J; Richardson, Des R

2009-01-01

Iron (Fe) chelators are used clinically for the treatment of Fe overload disease. Iron also plays a role in the pathology of many other conditions, and these potentially include the cardiotoxicity induced by catecholamines such as isoprenaline (ISO). The current study examined the potential of Fe chelators to prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO contains the classical catechol moiety that binds Fe and may form redox-active and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line, H9c2, which was treated with ISO in the presence or absence of the chelator, desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more effective than DFO, with the latter showing activity only at a high, clinically unachievable concentration. Further studies in vitro showed that interaction of ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting that this mechanism was not involved. Studies in vivo were initiated using rats pretreated intravenously with DFO or PCTH before subcutaneous administration of ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented catecholamine-induced mortality and reduced cardiotoxicity. This study demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo, demonstrating that Fe plays a role, in part, in the pathology observed.

Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.

PubMed

Fischer, Katrin; Ruiz, Henry H; Jhun, Kevin; Finan, Brian; Oberlin, Douglas J; van der Heide, Verena; Kalinovich, Anastasia V; Petrovic, Natasa; Wolf, Yochai; Clemmensen, Christoffer; Shin, Andrew C; Divanovic, Senad; Brombacher, Frank; Glasmacher, Elke; Keipert, Susanne; Jastroch, Martin; Nagler, Joachim; Schramm, Karl-Werner; Medrikova, Dasa; Collden, Gustav; Woods, Stephen C; Herzig, Stephan; Homann, Dirk; Jung, Steffen; Nedergaard, Jan; Cannon, Barbara; Tschöp, Matthias H; Müller, Timo D; Buettner, Christoph

2017-05-01

Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1 -/- and interleukin-4 receptor-α double-negative (Il4ra -/- ) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.

PubMed

Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E

2017-09-01

We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.

Neural Correlates of Impaired Reward-Effort Integration in Remitted Bulimia Nervosa.

PubMed

Mueller, Stefanie Verena; Morishima, Yosuke; Schwab, Simon; Wiest, Roland; Federspiel, Andrea; Hasler, Gregor

2018-03-01

The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward-processing deficits in remitted bulimia nervosa, the purpose of this study was to identify the role of catecholamine dysfunction and its relation to behavioral and neural reward-effort integration in bulimia nervosa. To investigate the interaction between catecholamine functioning and behavioral, and neural responses directly, 17 remitted bulimic (rBN) and 21 healthy individuals (HC) received alpha-methyl-paratyrosine (AMPT) over 24 h to achieve catecholamine depletion in a randomized, crossover study design. We used functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task to assess reward-effort integration in relation to catecholaminergic neurotransmission at the behavioral and neural level. AMPT reduced the ability to integrate rewards and efforts effectively in HC participants. In contrast, in rBN participants, the reduced reward-effort integration was associated with illness duration in the sham condition and unrelated to catecholamine depletion. Regarding neural activation, AMPT decreased the reward anticipation-related neural activation in the anteroventral striatum. This decrease was associated with the AMPT-induced reduction of monetary earning in HC in contrast to rBN participants. Our findings contributed to the theory of a desensitized dopaminergic system in bulimia nervosa. A disrupted processing of reward magnitudes and effort costs might increase the probability of maintenance of bulimic symptoms.

Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives.

PubMed

Sun, Wu-Ping; Li, Da; Lun, Yong-Zhi; Gong, Xiao-Jie; Sun, Shen-Xia; Guo, Ming; Jing, Li-Xin; Zhang, Li-Bin; Xiao, Fu-Cheng; Zhou, Shi-Sheng

2012-02-01

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N(1)-methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N(1)-methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamide-loading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells

PubMed Central

Ges, Igor A.; Brindley, Rebecca L.; Currie, Kevin P.M.; Baudenbacher, Franz J.

2013-01-01

Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped “cell traps”, each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion / repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time. PMID:24126415

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

PubMed Central

Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

Catecholaminergic contributions to vocal communication signals.

PubMed

Matheson, Laura E; Sakata, Jon T

2015-05-01

Social context affects behavioral displays across a variety of species. For example, social context acutely influences the acoustic and temporal structure of vocal communication signals such as speech and birdsong. Despite the prevalence and importance of such social influences, little is known about the neural mechanisms underlying the social modulation of communication. Catecholamines are implicated in the regulation of social behavior and motor control, but the degree to which catecholamines influence vocal communication signals remains largely unknown. Using a songbird, the Bengalese finch, we examined the extent to which the social context in which song is produced affected immediate early gene expression (EGR-1) in catecholamine-synthesising neurons in the midbrain. Further, we assessed the degree to which administration of amphetamine, which increases catecholamine concentrations in the brain, mimicked the effect of social context on vocal signals. We found that significantly more catecholaminergic neurons in the ventral tegmental area and substantia nigra (but not the central grey, locus coeruleus or subcoeruleus) expressed EGR-1 in birds that were exposed to females and produced courtship song than in birds that produced non-courtship song in isolation. Furthermore, we found that amphetamine administration mimicked the effects of social context and caused many aspects of non-courtship song to resemble courtship song. Specifically, amphetamine increased the stereotypy of syllable structure and sequencing, the repetition of vocal elements and the degree of sequence completions. Taken together, these data highlight the conserved role of catecholamines in vocal communication across species, including songbirds and humans. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Seasonal variation in plasma catecholamines and adipose tissue lipolysis in adult female green sea turtles (Chelonia mydas).

PubMed

Hamann, Mark; Limpus, Colin J; Whittier, Joan M

2003-02-15

We investigated three aspects of potential interrenal regulation of reproduction in female green sea turtles, Chelonia mydas. First, seasonal trends in plasma catecholamines were examined from female C. mydas at different stages of their reproductive cycles. Second, variation in catecholamine levels during a nesting season were analysed in relation to restraint time, and ecological variables such as nesting habitat, body size, and reproductive investment. Third, catecholamine and corticosterone (CORT) induced lipolysis was investigated with adipose tissue collected from gravid green turtles, using in vitro incubations. Plasma epinephrine (EPI) was lowest in non-vitellogenic (1.55 +/- 0.26 ng/ml) and post-breeding (1.57 +/- 0.22 ng/ml) females, and highest in courting females (2.87 +/- 0.28). Concentrations of norepinephrine (NE) and EPI were relatively constant throughout a nesting season, and not significantly related to restraint time, reproductive investment or nesting habitat. In vitro concentrations of CORT (>3 ng/ml) and NE (2 ng/ml) induced significant release of glycerol after 6h of incubation. Epinephrine tended to induce an antilipolytic affect at low concentrations (0.25 ng/ml) and a net lipolytic response at higher concentrations (>1 ng/ml). Our data suggest that EPI may play a role in regulating body condition during vitellogenesis, and maintaining energy stores during prolonged aphagia during courtship and nesting in female green sea turtles. Furthermore, we provide preliminary evidence that suggests that catecholamine production may be either down regulated or de-sensitised in gravid female C. mydas. Copyright 2003 Elsevier Science (USA)

Hypoxic alligator embryos: chronic hypoxia, catecholamine levels and autonomic responses of in ovo alligators.

PubMed

Eme, John; Altimiras, Jordi; Hicks, James W; Crossley, Dane A

2011-11-01

Hypoxia is a naturally occurring environmental challenge for embryonic reptiles, and this is the first study to investigate the impact of chronic hypoxia on the in ovo development of autonomic cardiovascular regulation and circulating catecholamine levels in a reptile. We measured heart rate (f(H)) and chorioallantoic arterial blood pressure (MAP) in normoxic ('N21') and hypoxic-incubated ('H10'; 10% O(2)) American alligator embryos (Alligator mississippiensis) at 70, 80 and 90% of development. Embryonic alligator responses to adrenergic blockade with propranolol and phentolamine were very similar to previously reported responses of embryonic chicken, and demonstrated that embryonic alligator has α and β-adrenergic tone over the final third of development. However, adrenergic tone originates entirely from circulating catecholamines and is not altered by chronic hypoxic incubation, as neither cholinergic blockade with atropine nor ganglionic blockade with hexamethonium altered baseline cardiovascular variables in N21 or H10 embryos. In addition, both atropine and hexamethonium injection did not alter the generally depressive effects of acute hypoxia - bradycardia and hypotension. However, H10 embryos showed significantly higher levels of noradrenaline and adrenaline at 70% of development, as well as higher noradrenaline at 80% of development, suggesting that circulating catecholamines reach maximal levels earlier in incubation for H10 embryos, compared to N21 embryos. Chronically elevated levels of catecholamines may alter the normal balance between α and β-adrenoreceptors in H10 alligator embryos, causing chronic bradycardia and hypotension of H10 embryos measured in normoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock

PubMed Central

Macarthur, Heather; Westfall, Thomas C.; Riley, Dennis P.; Misko, Thomas P.; Salvemini, Daniela

2000-01-01

A major feature of septic shock is the development of a vascular crisis characterized by nonresponsiveness to sympathetic vasoconstrictor agents and the subsequent irreversible fall in blood pressure. In addition, sepsis, like other inflammatory conditions, results in a large increase in the production of free radicals, including superoxide anions (O2⨪) within the body. Here we show that O2⨪ reacts with catecholamines deactivating them in vitro. Moreover, this deactivation would appear to account for the hyporeactivity to exogenous catecholamines observed in sepsis, because administration of a superoxide dismutase (SOD) mimetic to a rat model of septic shock to remove excess O2⨪ restored the vasopressor responses to norepinephrine. This treatment with the SOD mimetic also reversed the hypotension in these animals; suggesting that deactivation of endogenous norepinephrine by O2⨪ contributes significantly to this aspect of the vascular crisis. Indeed, the plasma concentrations of both norepinephrine and epinephrine in septic rats treated with the SOD mimetic were significantly higher than in untreated rats. Interestingly, the plasma concentrations for norepinephrine and epinephrine were inversely related to the plasma concentrations of adrenochromes, the product of the autoxidation of catecholamines initiated by O2⨪. We propose, therefore, that the use of a SOD mimetic represents a new paradigm for the treatment of septic shock. By removing O2⨪, exogenous and endogenous catecholamines are protected from autoxidation. As a result, both hyporeactivity and hypotension are reversed, generation of potentially toxic adrenochromes is reduced, and survival rate is improved. PMID:10944234

Evaluation and validation of a method for determining platelet catecholamine in patients with obstructive sleep apnea and arterial hypertension.

PubMed

Feres, Marcia C; Cintra, Fatima D; Rizzi, Camila F; Mello-Fujita, Luciane; Lino de Souza, Altay A; Tufik, Sergio; Poyares, Dalva

2014-01-01

Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions. In this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls. In the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension. A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05). Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluation of the effects of zilpateral hydrochloride supplementation on catecholamin response and other blood metabolites following a combined corticotropin releasing hormone and vasopressin challenge

USDA-ARS?s Scientific Manuscript database

The stress response of cattle supplemented with zilpaterol hydrochloride (ZH) has become a topic due to anecdotal claims of supplemented cattle responding poorly to stress. This study was designed to determine if differences exist in the catecholamine and blood metabolite response of ZH-supplemente...

Effect of quinine on the release of catecholamines from bovine cultured chromaffin cells.

PubMed Central

Tang, R.; Novas, M. L.; Glavinovic, M. I.; Trifaró, J. M.

1990-01-01

1. The effects of quinine on catecholamine release from cultured bovine chromaffin cells were studied. 2. Quinine (25-400 microM) produced a dose-related inhibition of catecholamine release in response to depolarizing concentrations (12.5-50 mM) of K+. 3. The inhibition of the secretory response to high K+ produced by quinine decreased with the increase in the extracellular concentration of Ca2+. 4. Stimulation of cultured chromaffin cells with 50 mM K+ produced a significant increase in Ca2+ influx. In the presence of 100 microM quinine a 54% inhibition of the K(+)-induced Ca2+ influx was observed. 5. Quinine treatment of chromaffin cell cultures produced a small but significant decrease in membrane resting potential and a less pronounced depolarization in response to 50 mM K+. 6. The results suggest that the inhibition of the K(+)-evoked release of catecholamines produced by quinine is at least partly due to a decrease in Ca2+ influx. Ca2+ influx is lower because quinine reduces the sensitivity of the membrane potential to changes in extracellular K+ but direct effects of quinine on Ca2+ channels cannot be excluded. PMID:2158846

Leisure Activities, Caregiving Demands, and Catecholamine Levels in Dementia Caregivers

PubMed Central

Chattillion, Elizabeth A.; Mausbach, Brent T.; Roepke, Susan K.; von Känel, Roland; Mills, Paul J.; Dimsdale, Joel E.; Allison, Matthew; Ziegler, Michael G.; Patterson, Thomas L.; Ancoli-Israel, Sonia; Grant, Igor

2012-01-01

This study examined whether satisfaction from leisure activities moderates the relationship between caregiving demands (i.e., hours per day spent caring for a spouse with dementia) and resting levels of the catecholamines norepinephrine (NE) and epinephrine (EPI). Spousal caregivers (N=107; mean age 73.95±8.12 years) were assessed in home for plasma levels of NE and EPI, amount of care provided, and leisure satisfaction. Regression was used to determine whether leisure satisfaction moderated the relationship between hours providing care per day and catecholamine levels. A significant interaction was found between hours caregiving and leisure satisfaction for NE, but not for EPI. Post hoc regressions were conducted for both NE and EPI. At low leisure satisfaction, time spent caring for a spouse was positively associated with plasma NE (β = .41; p = .005) and EPI (β = .44; p = .003). In contrast, at high levels of satisfaction, time caregiving was not significantly associated with plasma NE (β = −.08; p = .57) or EPI (β = .23; p = .12). These findings suggest that leisure satisfaction may protect caregivers from increases in catecholamines, which have been implicated in cardiovascular risk. Further support for these findings may impact psychological treatments for distressed caregivers. PMID:22149759

Lower catecholamine activity is associated with greater levels of anger in adults.

PubMed

Schwartz, Joseph A; Portnoy, Jill

2017-10-01

Previous research has revealed a consistent association between heart rate at rest and during stress and behavioral problems, potentially implicating autonomic nervous system (ANS) functioning in the etiological development of antisocial behavior. A complementary line of research has focused on the potential independent and interactive role of the two subsystems that comprise the ANS, the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS), on behavioral problems. The current study aims to contribute to the existing literature by examining the influence of heart rate (HR) reactivity, high-frequency heart rate variability (HF-HRV) reactivity, and catecholamine activity on a comprehensive measure of anger in a large, nationally-representative sample of adults from the United States. Results from a series of structural equation models (SEMs) revealed that catecholamine activity was most consistently linked to anger, while associations involving HR and HF-HRV reactivity were nonsignificant. Additional analyses revealed that HF-HRV did not significantly moderate the association between catecholamine activity and anger. These findings highlight the importance of SNS activity in the development of more reactive forms of aggression such as anger. Copyright © 2017 Elsevier B.V. All rights reserved.

Blood vessel adaptation to gravity in a semi-arboreal snake

NASA Technical Reports Server (NTRS)

Conklin, D. J.; Lillywhite, H. B.; Olson, K. R.; Ballard, R. E.; Hargens, A. R.

1996-01-01

The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessel were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress ( + 1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.

Evaluation of Endocrine Tests. C: glucagon and clonidine test in phaeochromocytoma.

PubMed

Bisschop, P H; Corssmit, E P M; Baas, S J; Serlie, M J; Endert, E; Wiersinga, W M; Fliers, E

2009-03-01

The diagnosis of phaeochromocytoma is based on the demonstration of catecholamine excess. Urine and plasma metanephrine measurements are highly sensitive tests for the diagnosis of phaeochromocytoma, but moderate elevations in metanephrines lack optimal specificity. In this study we aimed to evaluate the diagnostic value of additional tests, i.e. glucagon stimulation and clonidine suppression test, in patients with moderately elevated catecholamines and/or metanephrines. Patients with suspected phaeochromocytoma with moderately elevated catecholamines and/or metanephrines in plasma or urine were subjected to the glucagon stimulation and clonidine suppression test. The presence of phaeochromocytoma was confirmed by histology and the absence by a disease-free extended follow-up. Fifty-five patients were included. Phaeochromocytoma was diagnosed in 11 patients. The follow-up period in patients without phaeochromocytoma was 56 (19 to 154) months. The sensitivity of the glucagon test was 30% and the specificity 100%. The clonidine test had no discriminative power, because the area under the ROC curve was not significantly different from 0.5. The clonidine suppression test without normetanephrine measurements and the glucagon stimulation test are not sensitive enough to safely exclude phaeochromocytoma in patients with mildly elevated plasma or urine catecholamines.

L-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.

PubMed

Kelly, Alison U; Srivastava, Rajeev; Dow, Ellie; Davidson, D Fraser

2017-09-01

Neuroblastoma is the most common solid extracranial malignancy diagnosed in childhood. Clinical presentation is variable, and metastatic disease is common at diagnosis. Analyses of urinary catecholamines and their metabolites are commonly requested as a first-line investigation when clinical suspicion exists. Levodopa (L-Dopa) therapy is utilized as a treatment for a number of disorders in childhood, including Dopa-responsive dystonia. Neuroblastoma may mimic some of the clinical features of this disorder. L-Dopa can interfere with analysis of urinary catecholamines and their metabolites and complicate the interpretation of results. We present the cases of three children who were prescribed L-dopa at the time of analysis of urinary catecholamines and metabolites as a screen for neuroblastoma, but who did not have the disease. Comparison of their results with those from cases with true neuroblastoma reveal that it is impossible to reliably distinguish true neuroblastoma from L-Dopa therapy using these tests. We recommend that patients should be off L-dopa therapy, if possible when these tests are performed. These cases illustrate the importance of providing clinical details and drug history to the laboratory in order to avoid diagnostic confusion.

Regulation of galactokinase gene expression in Tetrahymena thermophila. II. Identification of 3,4-dihydroxyphenylalanine as a primary effector of adrenergic control of galactokinase expression.

PubMed

Ness, J C; Morse, D E

1985-08-25

Intracellular concentrations of catecholamines were determined in wild-type and mutant Tetrahymena thermophila, using the highly sensitive techniques of high-performance liquid chromatography and electro-chemical detection. Catecholamines were determined in these cell strains grown under various steady-state conditions, including those which initiate and maintain repression of galactokinase gene expression. Wild-type cells grown in defined minimal medium supplemented with 1% glycerol, exhibiting derepressed galactokinase synthesis, were found to contain considerable quantities of dopa (3,4-dihydroxyphenylalanine) and dopamine, but no detectable levels of either norepinephrine or epinephrine. Analyses of wild-type cells revealed a strong positive correlation between the internal concentration of dopa and expression of the galactokinase gene, both of which are regulated by exogenous carbohydrates, catecholamine agonists, or dibutyryl-cAMP; an analogous relationship between intracellular dopamine concentrations and galactokinase activity was not found. In addition, a correlation between intracellular dopa content and the phenotypic expression of galactokinase in various mutants deficient in the catecholamine biosynthetic pathway or in glucokinase further confirms the role of dopa as a primary effector in the regulation of galactokinase gene expression.

The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

PubMed Central

Kalsner, S

1976-01-01

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue. PMID:974389

Review of Stress and the Measurement of Stress in Marine Mammals

DTIC Science & Technology

2013-09-30

massey.ac.nz Award Number: N000141110434 LONG-TERM GOALS Physiological indicators of stress in wild marine mammals, the interrelationships between...hormones (GC), aldosterone (A), thyroid hormones (TH), and catecholamines within a free-ranging northern elephant seal population and its dependence upon...individuals per year). Serum samples will be processed for ACTH, cortisol, aldosterone , catecholamines (epinephrine, norepinephrine), and TH (T3

Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

DTIC Science & Technology

2011-09-30

massey.ac.nz Award Number: N000141110434 LONG-TERM GOALS Physiological indicators of stress in wild marine mammals, the interrelationships between...hormones (GC), aldosterone (A), thyroid hormones (TH), and catecholamines within a free-ranging northern elephant seal population and its...additional individuals per year). Serum samples will be processed for ACTH, cortisol, aldosterone , catecholamines (epinephrine, norepinephrine), and

PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

PubMed Central

Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

2013-01-01

Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle. Linked Article This article is commented on by Eschenhagen, pp 524–527 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12168 PMID:23489141

Reserpine-induced Reduction in Norepinephrine Transporter Function Requires Catecholamine Storage Vesicles

PubMed Central

Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A.

2010-01-01

Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5 min decreased [3H]NE uptake capacity, an effect characterized by a robust decrease in the Vmax of the transport of [3H]NE. As expected, reserpine did not displace the binding of [3H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [3H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [3H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca2+/Ca2+-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [3H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, α-methyl-p-tyrosine, increased [3H]NE uptake and eliminated the inhibitory effects of reserpine on [3H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca2+-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. PMID:20176067

Mechanisms involved in cardiac sensitization by volatile anesthetics: general applicability to halogenated hydrocarbons?

PubMed

Himmel, Herbert M

2008-01-01

An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I(Ks), as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar mechanisms as volatile anesthetics. Experimental approaches for further investigation of these sensitization mechanisms by selected halocarbons are suggested.

The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

PubMed

Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

2014-12-07

A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; P<.0001). The plasma leptin levels were higher under catecholamine depletion compared with placebo in the whole sample (treatment effect; P=.0004). This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with remitted bulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Telomere length is inversely correlated with urinary stress hormone levels in healthy controls but not in un-medicated depressed individuals-preliminary findings.

PubMed

Fair, Brittany; Mellon, Synthia H; Epel, Elissa S; Lin, Jue; Révész, Dóra; Verhoeven, Josine E; Penninx, Brenda W; Reus, Victor I; Rosser, Rebecca; Hough, Christina M; Mahan, Laura; Burke, Heather M; Blackburn, Elizabeth H; Wolkowitz, Owen M

2017-08-01

Leukocyte telomere length (LTL) is a biomarker of cellular aging affected by chronic stress. The relationship of LTL to the stress hormones, cortisol and catecholamines, is unclear, as are possible differences between healthy controls (HC) and individuals with Major Depressive Disorder (MDD). This small pilot study is the first to examine the relationship between cortisol, catecholamines and LTL specifically in un-medicated MDD in comparison with HC. Participants included 16 un-medicated MDD subjects and 15 HC for assay of LTL, 12-hour overnight urinary free cortisol and catecholamine levels. LTL, cortisol and catecholamine levels did not significantly differ between groups. In HC, a hierarchical regression analysis indicated that higher levels of cortisol were correlated with shorter LTL (p=0.003) above and beyond age and sex. Higher catecholamine levels were nearly-significant with shorter LTL (p=0.055). Neither hormone was correlated with shorter LTL in MDD (p's>0.28). To assess a possible cumulative effect of stress hormone activation, a summary score was calculated for each subject based on the number of stress hormone levels above the median for that group (HC or MDD). A significant inverse graded relationship was observed between LTL and the number of activated systems in HC (p=0.001), but not in MDD (p=0.96). This pilot study provides preliminary evidence that stress hormone levels, especially cortisol, are inversely related to LTL in HC, but not in un-medicated MDD. Clarification of these relationships in larger samples could aid in understanding differential mechanisms underlying stress-related cellular aging in healthy and depressed populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons.

PubMed

Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Powers, Bethany R; Ritter, Sue

2014-02-15

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons

PubMed Central

Wang, Qing; Dinh, Thu T.; Powers, Bethany R.; Ritter, Sue

2013-01-01

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component. PMID:24381177

The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure

PubMed Central

Fargali, Samira; Garcia, Angelo L.; Sadahiro, Masato; Jiang, Cheng; Janssen, William G.; Lin, Wei-Jye; Cogliani, Valeria; Elste, Alice; Mortillo, Steven; Cero, Cheryl; Veitenheimer, Britta; Graiani, Gallia; Pasinetti, Giulio M.; Mahata, Sushil K.; Osborn, John W.; Huntley, George W.; Phillips, Greg R.; Benson, Deanna L.; Bartolomucci, Alessandro; Salton, Stephen R.

2014-01-01

Secretion of proteins and neurotransmitters from large dense core vesicles (LDCVs) is a highly regulated process. Adrenal LDCV formation involves the granin proteins chromogranin A (CgA) and chromogranin B (CgB); CgA- and CgB-derived peptides regulate catecholamine levels and blood pressure. We investigated function of the granin VGF (nonacronymic) in LDCV formation and the regulation of catecholamine levels and blood pressure. Expression of exogenous VGF in nonendocrine NIH 3T3 fibroblasts resulted in the formation of LDCV-like structures and depolarization-induced VGF secretion. Analysis of germline VGF-knockout mouse adrenal medulla revealed decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content and circulating plasma epinephrine, and decreased adrenal CgB. These neurochemical changes in VGF-knockout mice were associated with hypertension. Germline knock-in of human VGF1–615 into the mouse Vgf locus rescued the hypertensive knockout phenotype, while knock-in of a truncated human VGF1–524 that lacks several C-terminal peptides, including TLQP-21, resulted in a small but significant increase in systolic blood pressure compared to hVGF1–615 mice. Finally, acute and chronic administration of the VGF-derived peptide TLQP-21 to rodents decreased blood pressure. Our studies establish a role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure.—Fargali, S., Garcia, A. L., Sadahiro, M., Jiang, C., Janssen, W. G., Lin, W.-J., Cogliani, V., Elste, A., Mortillo, S., Cero, C., Veitenheimer, B., Graiani, G., Pasinetti, G. M., Mahata, S. K., Osborn, J. W., Huntley, G. W., Phillips, G. R., Benson, D. L., Bartolomucci, A., Salton, S. R. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. PMID:24497580

The action of volatile anaesthetics on stimulus-secretion coupling in bovine adrenal chromaffin cells.

PubMed Central

Pocock, G.; Richards, C. D.

1988-01-01

1. The action of four volatile anaesthetics, ethrane, halothane, isoflurane and methoxyflurane on stimulus-secretion coupling has been studied in isolated bovine adrenal medullary cells. All four agents inhibited the secretion of adrenaline and noradrenaline evoked by 500 microM carbachol at concentrations within the anaesthetic range. Total catecholamine secretion induced by stimulation with 77 mM potassium was also inhibited but at higher concentrations. All four agents inhibited the 45Ca influx evoked by stimulation with 500 microM carbachol and the 45Ca influx in response to K+-depolarization. 2. When total catecholamine secretion in response to potassium or carbachol was modulated by varying extracellular calcium or by adding halothane or methoxyflurane to the incubation medium, the amount of catecholamine secretion for a given Ca2+ entry was the same. 3. The action of methoxyflurane on the relationship between intracellular free Ca and exocytosis was examined using electropermeabilised cells, which were suspended in solutions containing a range of concentrations of ionised calcium between 10(-8) and 10(-4)M. The anaesthetic had no effect on the activation of exocytosis by intracellular free calcium. 4. Halothane and methoxyflurane inhibited the carbachol-induced secretion of catecholamines in a non-competitive manner. 5. Halothane and methoxyflurane inhibited the increase in 22Na influx evoked by carbachol. For halothane and methoxyflurane this inhibition of Na influx appears to be sufficient to account for the inhibition of the evoked catecholamine secretion. 6. We conclude that the volatile anaesthetics ethrane, halothane, isoflurane and methoxyflurane inhibit the secretion of adrenaline and noradrenaline induced by carbachol at concentrations that lie within the range encountered during general anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2464384

Occupational EMF exposure from radar at X and Ku frequency band and plasma catecholamine levels.

PubMed

Singh, Sarika; Kapoor, Neeru

2015-09-01

Workers in certain occupations such as the military may be exposed to technical radiofrequency radiation exposure above current limits, which may pose a health risk. The present investigation intended to find the effect of chronic electromagnetic field (EMF) exposure from radar on plasma catecholamines in the military workforce. In the study, 166 male personnel selected randomly were categorized into three groups: control (n = 68), exposure group-I (X-band, 8-12 GHz, n = 40), and exposure group-II (Ku-band, 12.5-18 GHz, n = 58). The three clusters were further divided into two groups according to their years of service (YOS) (up to 9 years and ≥10 years) to study the effect of years of radar exposure. Enzyme immunoassay was employed to assess catecholamine concentrations. EMF levels were recorded at different occupational distances from radar. Significant adrenaline diminution was registered in exposure group-II with no significant difference in exposure group-I when both groups were weighed against control. Nor-adrenaline and dopamine levels did not vary significantly in both exposure groups when compared to controls. Exposure in terms of YOS also did not yield any significant alteration in any of the catecholamines and in any of the exposure groups when compared with their respective control groups. The shift from baseline catecholamine values due to stress has immense significance for health and well-being. Their continual alteration may prove harmful in due course. Suitable follow-up studies are needed to further strengthen these preliminary observations and for now, exposures should be limited as much as possible with essential safeguards. © 2015 Wiley Periodicals, Inc.

Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.

PubMed

Pasquali, Daniela; Rossi, Valentina; Conzo, Giovanni; Pannone, Giuseppe; Bufo, Pantaleo; De Bellis, Annamaria; Renzullo, Andrea; Bellastella, Giuseppe; Colao, Annamaria; Vallone, Gianfranco; Bellastella, Antonio; Sinisi, Antonio A

2008-06-01

Surgery is the primary therapy for pheochromocytoma (PHEO), a catecholamine-producing tumor. Benign and malignant PHEO could develop recurrences, and the intraoperative risk of recurrent PHEO is an important unresolved issue. Non-surgical treatments of PHEO recurrence would therefore better prepare patients for reintervention as well as provide them with palliative management. We investigated the effects of the new somatostatin analog (pasireotide) SOM230 versus octreotide (OCT) in primary PHEO cell cultures (Pheo-c). Pheo-c from six benign surgical samples were set up and characterized by immunocytochemistry. Real-time PCR, using both PHEO tissues and Pheo-c, showed different levels of somatostatin receptor(1-5) mRNA expression. Cells treated with various doses of OCT or SOM230 for 48 and 72 h were analyzed to assess their effects on cell proliferation and apoptosis and catecholamine levels. Even if reduction of cell viability was observed in Pheo-c treated for 48 h with either OCT or SOM230 and this effect increased after 72 h, a more significant inhibition of cell growth as well as a significantly higher induction of apoptosis was seen in Pheo-c treated with SOM230 versus OCT. In particular, apoptosis in Pheo-c was detected after 48 h and was associated with increased expression and activation of caspase-3 and cleaved poly(ADP-ribose) polymerase. OCT 10(-6) M and SOM230 10(-7) M significantly reduced catecholamine levels. Our results indicate that while both OCT and SOM230 modulate cell growth and apoptosis and catecholamine levels in Pheo-c through specific receptors, SOM230 is more effective. This improves our knowledge on the mechanism of SOM230 action in PHEO and supports a possible therapeutic use in benign PHEO recurrence.

Growth Stimulation by Catecholamines in Plant Tissue/Organ Cultures 1

PubMed Central

Protacio, Calixto M.; Dai, Yao-ren; Lewis, Eldrin F.; Flores, Hector E.

1992-01-01

Addition of catecholamines at micromolar concentrations caused a dramatic stimulation of growth of tobacco (Nicotiana tabacum) thin cell layers (TCLs) and Acmella oppositifolia “hairy” root cultures. A threefold increase in the rate of ethylene evolution was observed in the catecholamine-treated explants. Aminooxyacetic acid and silver thiosulfate, inhibitors of ethylene biosynthesis and action, respectively, reduced the growth-promoting effect of dopamine. However, these compounds alone could also inhibit the growth of the TCL explants. When ethylene in the culture vessel was depleted by trapping with mercuric perchlorate, dopamine-stimulated growth was still obtained, suggesting that ethylene does not mediate the dopamine effect. Dopamine potentiated the growth of TCLs grown in Murashige and Skoog medium supplemented with indoleacetic acid (IAA) and kinetin. When IAA was replaced by 2,4-dichlorophenoxyacetic acid, dopamine addition showed no growth-promoting effect. Instead, 2,4-dichlorophenoxyacetic acid stimulated the growth of TCL explants to the same extent as that obtained with IAA plus dopamine. Because synthetic auxins do not appear to be substrates for IAA oxidizing enzymes, we hypothesized that catecholamines exert their effect by preventing IAA oxidation. Consistent with this explanation, dopamine (25 micromolar) inhibited IAA oxidase activity by 60 to 100% in crude enzyme extracts from tobacco roots and etiolated corn coleoptiles, but had no effect on peroxidase activity in the same extracts. Furthermore, addition of dopamine to TCL cultures resulted in a fourfold reduction in the oxidative degradation of [1-14C]IAA fed to the explants. Because the growth enhancement by catecholamines is observed in both IAA-requiring and IAA-independent cultures, we suggest that these aromatic amines may have a role in the regulation of IAA levels in vivo. ImagesFigure 2 PMID:16668653

Modulation of key reactions of the catecholamine metabolism by extracts from Eschscholtzia californica and Corydalis cava.

PubMed

Kleber, E; Schneider, W; Schäfer, H L; Elstner, E F

1995-02-01

Aqueous-alcoholic extracts from Eschscholtzia californica inhibit the enzymatic degradation of catecholamines as well as the synthesis of adrenaline, whereas aqueous-ethanolic extracts from Corydalis cava enhance the chemical oxidation of adrenaline and the synthesis of melanine from dihydroxyphenylalanine (DOPA). Both extracts dramatically shorten the lag phase in the catalysis of phenolase probably due to their o-diphenol content, where the Corydalis extracts are 10 times more active than the Eschscholtzia preparations. Dopamine beta-hydroxylase and monoamine oxidase (MAO-B) are especially inhibited by Eschscholtzia extracts. Diamine oxidases are inhibited by both preparations to a similar extent. The results of this study may be interpreted as a cooperative function of the two preparations in establishing and preserving high catecholamine levels thus explaining their sedative, antidepressive and hypnotic activities.

Observations on cardiovascular and neuroendocrine disturbance in the Guillain-Barré syndrome

PubMed Central

Davies, A. G.; Dingle, H. R.

1972-01-01

Cardiovascular disturbances were found to be a common feature of patients with the Guillian-Barré syndrome who were severely paralysed, requiring assisted ventilation. Glycosuria was noted in association with these disturbances, and in five patients investigated we found impaired glucose tolerance tests at the height of the paralysis. Catecholamine and 17-hydroxycorticosteroid urinary excretions were found to be high in four patients investigated when the neuropathy was most severe, and in one patient plasma cortisol levels were high with loss of diurnal variation. With recovery from paralysis cardiovascular disturbances became less marked, catecholamine and 17-hydroxycorticosteroid urinary excretions reverted to normal, glucose tolerance improved but remained abnormal in three patients during the period of observation. It is suggested that increased levels of catecholamines and cortisol contributed to the development of impaired glucose tolerance and cardiovascular disturbances. PMID:4113954

Multifunctional Polyphenols- and Catecholamines-Based Self-Defensive Films for Health Care Applications.

PubMed

Dhand, Chetna; Harini, Sriram; Venkatesh, Mayandi; Dwivedi, Neeraj; Ng, Alice; Liu, Shouping; Verma, Navin Kumar; Ramakrishna, Seeram; Beuerman, Roger W; Loh, Xian Jun; Lakshminarayanan, Rajamani

2016-01-20

In an era of relentless evolution of antimicrobial resistance, there is an increasing demand for the development of efficient antimicrobial coatings or surfaces for food, biomedical, and industrial applications. This study reports the laccase-catalyzed room-temperature synthesis of mechanically robust, thermally stable, broad spectrum antimicrobial films employing interfacial interactions between poly(vinyl alcohol), PVA, and 14 naturally occurring catecholamines and polyphenols. The oxidative products of catecholamines and polyphenols reinforce the PVA films and also alter their surface and bulk properties. Among the catecholamines-reinforced films, optimum surface and bulk properties can be achieved by the oxidative products of epinephrine. For polyphenols, structure-property correlation reveals an increase in surface roughness and elasticity of PVA films with increasing number of phenolic groups in the precursors. Interestingly, PVA films reinforced with oxidized/polymerized products of pyrogallol (PG) and epinephrine (EP) display potent antimicrobial activity against pathogenic Gram-positive and Gram-negative strains, whereas hydroquinone (HQ)-reinforced PVA films display excellent antimicrobial properties against Gram-positive bacteria only. We further demonstrate that HQ and PG films retain their antimicrobial efficacy after steam sterilization. With an increasing trend of giving value to natural and renewable resources, our results have the potential as durable self-defensive antimicrobial surfaces/films for advanced healthcare and industrial applications.

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

NASA Technical Reports Server (NTRS)

Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

1993-01-01

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

Prevention moderates associations between family risks and youth catecholamine levels.

PubMed

Brody, Gene H; Yu, Tianyi; Chen, Edith; Miller, Gregory E

2014-11-01

The purpose of this study was to establish, using a quasi-experimental design, whether 2 family risk factors, parental psychological dysfunction and nonsupportive parenting, during preadolescence could longitudinally predict elevated sympathetic nervous system (SNS) activity 9 years later, and to determine whether participation in an efficacious family centered prevention program could moderate these associations if they emerged. Rural African American preadolescents (N = 476) were assigned randomly to the Strong African American Families (SAAF) program or to a control condition. When youths were 11 years of age (M = 11.2 years), primary caregivers provided data on their own depressive symptoms and self-esteem, and youths provided data on their receipt of nonsupportive parenting. When the youths were 20 years of age, indicators of SNS activity, the catecholamines epinephrine and norepinephrine, were assayed from their overnight urine voids. Parental psychological dysfunction and nonsupportive parenting forecast elevated catecholamine levels for youths in the control condition, but not for those in the SAAF condition. The demonstration that a prevention program can induce reduction of catecholamine levels is important from both theoretical and public health perspectives, because it shows that the developmental progression from family risk factors to heightened sympathetic nervous system activity is not immutable. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Critical study of common conditions of storage of glucocorticoids and catecholamines in 24-h urine collected during resting and exercising conditions.

PubMed

Gouarne, C; Foury, A; Duclos, M

2004-10-01

Except immediate freezing of the samples, no practical method has been validated for preservation of glucocorticoids and catecholamines in 24-h urine collection. Furthermore, the influence of urine storage at bladder temperature during periods of different lengths and the effect of prior exercise on preservation of these hormones in the bladder have not been investigated until now. Ten healthy volunteers collected their urine both after a resting and after an exercise session. Urine was aliquoted into tubes which were stored during 24 h in the presence or in the absence of preservatives and at different temperatures. Two samples were stored either 3 or 9 h at 37 degrees C (bladder temperature) without additive. When collecting 24-h urine samples for glucocorticoids determination, sample can be stored at room temperature during the 24-h collection period without compromising glucocorticoids preservation. When collecting 24-h urine samples for catecholamines determination, samples have to be chilled without preservative during the whole of the collection period. If the samples have to be stored at room temperature, HCl should be used. Moreover, we report for the first time that catecholamines can be degraded in the bladder and therefore that subjects should urinate every 3 h during either a resting or an exercising day.

Effect of betel quid on catecholamine secretion from adrenal chromaffin cells.

PubMed

Wang, C K; Hwang, L S

1997-10-01

Health damage and environmental pollution are serious problems caused by betel quid chewing in Taiwan. Many people acquire the habit of chewing betel quid due to its physiological effects, including increased stamina and a general feeling of well-being. In this study, a sympathetic model system of adrenal chromaffin cells and sensory evaluation were used to examine the physiological effects of betel quid and the interaction of all the ingredients (areca fruit, Piper betle inflorescence and red time paste) in betel quid. Physiological effects of cardioacceleration, a slightly drunk feeling, sweating and salivation occurred during the chewing of betel quid (a mixture of areca fruit, Piper betle inflorescence and red lime paste) and a mixture of areca fruit and red lime paste. Both induced much more basal catecholamine secretion from adrenal chromaffin cells than did other ingredients and combinations of ingredients. It was evident that the responses in the sympathetic model system were closely correlated with the physiological feeling of well-being. The inhibitory effects of all the chewing juices on catecholamine secretion evoked by carbachol and a high concentration of potassium (high K+) showed that they perhaps affected the calcium influx through voltage-sensitive channels or the steps involved in secretion after calcium entry to stimulate basal catecholamine secretion from chromaffin cells.

Renalase prevents AKI independent of amine oxidase activity.

PubMed

Wang, Ling; Velazquez, Heino; Moeckel, Gilbert; Chang, John; Ham, Ahrom; Lee, H Thomas; Safirstein, Robert; Desir, Gary V

2014-06-01

AKI is characterized by increased catecholamine levels and hypertension. Renalase, a secretory flavoprotein that oxidizes catecholamines, attenuates ischemic injury and the associated increase in catecholamine levels in mice. However, whether the amine oxidase activity of renalase is involved in preventing ischemic injury is debated. In this study, recombinant renalase protected human proximal tubular (HK-2) cells against cisplatin- and hydrogen peroxide-induced necrosis. Similarly, genetic depletion of renalase in mice (renalase knockout) exacerbated kidney injury in animals subjected to cisplatin-induced AKI. Interestingly, compared with the intact renalase protein, a 20-amino acid peptide (RP-220), which is conserved in all known renalase isoforms, but lacks detectable oxidase activity, was equally effective at protecting HK-2 cells against toxic injury and preventing ischemic injury in wild-type mice. Furthermore, in vitro treatment with RP-220 or recombinant renalase rapidly activated Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinases and downregulated c-Jun N-terminal kinase. In summary, renalase promotes cell survival and protects against renal injury in mice through the activation of intracellular signaling cascades, independent of its ability to metabolize catecholamines, and we have identified the region of renalase required for these effects. Renalase and related peptides show potential as therapeutic agents for the prevention and treatment of AKI. Copyright © 2014 by the American Society of Nephrology.

PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

PubMed Central

Pacak, Karel

2012-01-01

The WHO classification of endocrine tumors defines pheochromocytoma as a tumor arising from chromaffin cells in the adrenal medulla — an intra-adrenal paraganglioma. Closely related tumors of extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. Almost all pheochromocytomas and paragangliomas produce catecholamines. The concentrations of catecholamines in pheochromocytoma tissues are enormous, potentially creating a volcano that can erupt at any time. Significant eruptions result in catecholamine storms called “attacks” or “spells”. Acute catecholamine crisis can strike unexpectedly, leaving traumatic memories of acute medical disaster that champions any intensive care unit. A very well-defined genotype-biochemical phenotype relationship exists, guiding proper and cost-effective genetic testing of patients with these tumors. Currently, the production of norepinephrine and epinephrine is optimally assessed by the measurement of their O-methylated metabolites, normetanephrine or metanephrine, respectively. Dopamine is a minor component, but some paragangliomas produce only this catecholamine or this together with norepinephrine. Methoxytyramine, the O-methylated metabolite of dopamine, is the best biochemical marker of these tumors. In those patients with equivocal biochemical results, a modified clonidine suppression test coupled with the measurement of plasma normetanephrine has recently been introduced. In addition to differences in catecholamine enzyme expression, the presence of either constitutive or regulated secretory pathways contributes further to the very unique mutation-dependent catecholamine production and release, resulting in various clinical presentations. Oxidative stress results from a significant imbalance between levels of prooxidants, generated during oxidative phosphorylation, and antioxidants. The gradual accumulation of prooxidants due to metabolic oxidative stress results in proto-oncogene activation, tumor suppressor gene inactivation, DNA damage, and genomic instability. Since the mitochondria serves as the main source of prooxidants, any mitochondrial impairment leads to severe oxidative stress, a major outcome of which is tumor development. In terms of cancer pathogenesis, pheochromocytomas and paragangliomas represent tumors where the oxidative phosphorylation defect due to the mutation of succinate dehydrogenase is the cause, not a consequence, of tumor development. Any succinate dehydrogenase pathogenic mutation results in the shift from oxidative phosphorylation to aerobic glycolysis in the cytoplasm (also called anaerobic glycolysis if hypoxia is the main cause of such a shift). This phenomenon, also called the Warburg effect, is well demonstrated by a positive [18F]-fluorodeoxyglycose positron emission tomography scan. Microarray studies, genome-wide association studies, proteomics and protein arrays, metabolomics, transcriptomics, and bioinformatics approaches will remain powerful tools to further uncover the pathogenesis of these tumors and their unique markers, with the ultimate goal to introduce new therapeutic options for those with metastatic or malignant pheochromocytoma and paraganglioma. Soon oxidative stress will be tightly linked to a multistep cancer process in which the mutation of various genes (perhaps in a logistic way) ultimately results in uncontrolled growth, proliferation, and metastatic potential of practically any cell. Targeting the mTORC, IGF-1, HIF and other pathways, topoisomerases, protein degradation by proteosomes, balancing the activity of protein kinases and phosphatases or even synchronizing the cell cycle before any exposure to any kind of therapy will soon become a reality. Facing such a reality today will favor our chances to “beat” this disease tomorrow. PMID:21615192

CDCA7L and Mechanisms of Increased Male Bias in Glioma

DTIC Science & Technology

2016-05-01

interested in whether NF1 mutations affect the molecular function of CDCA7L and whether sex -specific treatments may be more effective for treating these...astrocyte phenotypes, and catecholamine levels. 2. Keywords Neurofibromatosis type 1 CDCA7L astrocytoma glioblastoma MAO catecholamines sex ...2015 NF Research Symposium as described under (6) Products. We are revising a manuscript based on his findings so far on the sex -specific activity

Cardiogenic shock with basal transient left ventricular ballooning (Takotsubo-like cardiomyopathy) as first presentation of pheochromocytoma.

PubMed

Di Palma, Gisella; Daniele, Gian P; Antonini-Canterin, Francesco; Piazza, Rita; Nicolosi, Gian L

2010-07-01

Pheochromocytoma is a rare tumor that produces a distant effect by secretion of catecholamines. This tumor usually presents with hypertension and palpitations but it may also cause cardiogenic shock because of catecholamine-induced myocardial dysfunction. We describe a rare case of Takotsubo-like cardiomyopathy as first manifestation of pheochromocytoma with an unusual onset characterized by severe hypotension and transient basal left ventricular ballooning ('inverted' Takotsubo-like cardiomyopathy).

Obstructive sleep apnea presenting as pseudopheochromocytoma

PubMed Central

Marmouch, Hela; Arfa, Sondes; Graja, Sameh; Slim, Tensim; Khochtali, Ines

2016-01-01

A 52-year-old female with a history of poorly controlled resistant hypertension was admitted to our hospital with severe hypertension. She had a history of fatigue and intermittent episodes of palpitations. Laboratory evaluation was significant for elevated 24-h urinary catecholamine levels (3,5 times the upper normal levels). This case was presenting with a clinical and biochemical picture indistinguishable from that of pheochromocytoma. However, neither computed tomography nor meta-iodo-benzyl-guanidine scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. Our patient was screened with full polysomnography because of heavy snoring, daytime somnolence and obesity. It revealed severe obstructive sleep apnea syndrome. After three months of continuous positive airway pressure therapy, the patient experienced resolution of his presenting symptoms, improved blood pressure control and normalization of his urinary catecholamine levels. This case highlights sleep disordered breathing as a potentially reversible cause of pseudo-pheochromocytoma. PMID:27217898

Myocardial correlates of helium-cold induction and maintenance of hypothermia.

NASA Technical Reports Server (NTRS)

Anderson, G. L.; Prewitt, R., Jr.; Musacchia, X. J.

1971-01-01

Hypothermia was induced in the golden hamster Mesocricetus auratus, using the helium-cold method. The first group of hamsters was sacrificed immediately after induction to rectal temperature 7 C, a second group was sacrificed after being maintained at a body temperature of 7 C for 18-24 hr, and a third group consisted of unexposed controls. The hearts were excised and the ventricles analyzed for hypoxic damage, glycogen, and catecholamines. In the short-term hypothermic animals, resting tension was increased while peak isometric tension, generated tension after 10 min of anoxic exposure, glycogen, and catecholamines were all reduced. All of the functional parameters recovered in the long-term hypothermic group, while glycogen and catecholamines showed a trend toward recovery. It is concluded that myocardial hypoxia develops during induction into hypothermia when using the helium-cold method. This effect is reversible and hypoxic damage does not increase as the hypothermic exposure is prolonged.

Sympathetic neural control of indoleamine metabolism in the rat pineal gland

NASA Technical Reports Server (NTRS)

Lynch, H. J.; Hsuan, M.; Wurtman, R. J.

1975-01-01

The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

Effect of consecutive cooling and immobilization on catecholamine metabolism in rat tissues

NASA Technical Reports Server (NTRS)

Matlina, E. S.; Waysman, S. M.; Zaydner, I. G.; Kogan, B. M.; Nozdracheva, L. V.

1979-01-01

The combined effect of two stressor stimuli--cooling and immobilization--acting successively on the sympathetic-adrenaline system was studied experimentally in rats that were cooled for 8 hours at 7 C on the first day and immobilized for 6 hours on the next day. The biochemical and histochemical methods used and the experimental technique involved are described in detail. The following conclusions were formulated: (1) the successive action of cooling and immobilization results in a stronger decrease in the adrenaline and noradrenaline content in the adrenal gland than that which could be due to a simple summation of the cooling and immobilization effects; (2) successive cooling and immobilization are followed by activation of catecholamine synthesis in the adrenal gland; and (3) 1-DOPA administration (45 mg/kg 3 times in 2 days) intraabdominally activated catecholamine synthesis in the adrenal glands in both the control and test animals.

Effect of 3-Day Bed Rest on the Basal Sympathetic Activity and Responsiveness of this System to Physiological Stimuli In Athletes and Sedentary Subjects

NASA Technical Reports Server (NTRS)

Smorawinski, Jerzy; Adrian, Jacek; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Greenleaf, John E.; Dalton, P. Bonnie (Technical Monitor)

2002-01-01

The aims of this study were: (1) to examine the effect of three days of bed rest (BR) on basal plasma epinephrine [E] and norepinephrine [NE] and the catecholamine responses to various physiological stimuli, and (2) to find out whether previous physical activity modifies effects of BR. In the first series, 29 young men (11 sedentary students, 8 endurance and 10 strength trained athletes) were submitted to oral glucose tolerance test in supine position and to active orthostatic test before and after 3 days of BR. Plasma [E] and [NE] were measured after overnight fast (basal condition), at 60, 120 and 180 min after glucose ingestion (70 a), and at the 8th min of unsupported standing. In the second series, other 22 subjects (12 sedentary students, 10 endurance and 10 strength trained athletes) were submitted to 2 min cold pressor test (CPT) and exercise. Plasma E and NE were determined in the supine position after overnight fast and at 60th and 120th s of hand cooling. Then, after breakfast followed by 2-3 hour sitting, the subjects performed cycle ergometer exercise with workload increasing until volitional exhaustion. Plasma [E] and [NE] were determined at the end of each load. Plasma catecholamines were determined made radioenzymatically. After BR, basal plasma [NE] was decreased in endurance and strength athletes (p<0.01) but not in sedentary subjects. In neither group BR affected the basal [E]. Responses of both catecholamines to glucose load were diminished after BR in all three groups (p<0.05) but the effect was most pronounced in the endurance athletes. All subjects tolerated well 8-min standing although their heart rate response was increased after BR. Plasma catecholamine responses standing were not significantly affected by BR in either group but the plasma [NE] and [E] during standing were lowered after BR in endurance athletes (p<0.01). BR did not affect blood pressure and catecholamine responses to CPT. The pre- and post-exercise plasma catecholamines were similar before and after BR although the subjects achieved lower maximal loads after BR. In endurance athletes the threshold for plasma NA rise occurred at lower work intensity after than before BR (p<0.05).

Relationship of Sleep Quantity and Quality with 24-Hour Urinary Catecholamines and Salivary Awakening Cortisol in Healthy Middle-Aged Adults

PubMed Central

Zhang, Jihui; Ma, Ronald C.W.; Kong, Alice P.S.; So, Wing Yee; Li, Albert M.; Lam, Sui Ping; Li, Shirley Xin; Yu, Mandy W.M.; Ho, Chung Shun; Chan, Michael H.M.; Zhang, Bin; Wing, Yun Kwok

2011-01-01

Objectives: a. Explore the stability in sleep/wake patterns of middle-aged adults over a 3-year follow-up period. b. Explore the relationship between objectively measured sleep indices, urinary catecholamines, and salivary cortisol. Design: Naturalistic follow-up for sleep/wake patterns (n = 114) by 2-week sleep log and cross-sectional design for objective sleep assessments and hormonal measures (n = 96) at follow-up period nearly 3 years after baseline measurements. Setting: Community Participants: Healthy middle-aged adults Interventions: N/A Measurements and Results: There were high correlations between baseline and follow-up period (2.6 ± 0.5 years) on sleep/wake patterns (r = 0.6–0.79) as measured by 2-week sleep log. For wave 2 cross-sectional study, objective poor sleepers (3-day actigraphy sleep efficiency < 85%) had a higher 24-h urinary norepinephrine (NE) level (205.7 ± 105 nmol/d vs 162.1 ± 55.6 nmol/d, P = 0.03) and a nearly significantly higher 24-h urinary epinephrine (E) level (P = 0.12) than good sleepers. There were no differences in 3-day mean salivary awakening cortisol and 24-h urinary catecholamines (NE and E) between short and normal/long sleepers. Linear regression results, however, showed that shorter time in bed and actual sleep time, longer sleep onset latency, and lower sleep efficiency were correlated with higher 24-h urinary E and NE (all P < 0.05) but not salivary cortisol. The effect of poor sleep quality on 24-h urinary catecholamines was stronger in males than females. Conclusions: Increased sympathetic activity as measured by 24-h urinary catecholamines might play a critical role in the pathogenesis mediating the relationship of insufficient sleep (quantity and quality) with subsequent cardiovascular and metabolic complications. Salivary awakening cortisol was not associated with sleep quantity and quality in healthy middle-aged adults. Citation: Zhang J; Ma RCW; Kong APS; So WY; Li AM; Lam SP; Li SX; Yu MWM; Ho CS; Chan MHM; Zhang B; Wing YK. Relationship of sleep quantity and quality with 24-hour urinary catecholamines and salivary awakening cortisol in healthy middle-aged adults. SLEEP 2011;34(2):225-233. PMID:21286244

Catecholamines release mediators in the opossum oesophageal circular smooth muscle.

PubMed Central

Daniel, E E; Jager, L P; Jury, J

1987-01-01

1. Effects of catecholamines applied exogenously to the circular smooth muscle layer of the body of the oesophagus of the opossum (Didelphis marsupialis) were studied, simultaneously measuring changes in the membrane potential, the membrane conductance and the contractility of the muscle, using the double sucrose-gap technique. 2. Superfusion of the smooth muscle with Krebs solution at 27 degrees C containing dopamine (10(-6)-10(-4) M) dose-dependently caused a hyperpolarization of the smooth muscle cells and an increased membrane resistance followed after gradual repolarization by oscillations of the membrane potential, often accompanied by muscle action potentials. During the hyperpolarization, the tendency for the membrane potential to sag during prolonged application of hyperpolarizing currents was reduced and the 'off' depolarization following such currents was increased. This muscle did not develop active tension prior to treatment; it therefore did not relax during the hyperpolarizations, but contracted following the depolarized phase of oscillations. 3. The non-adrenergic, non-cholinergic nerve-mediated inhibitory junction potential (i.j.p.) showed a small reduction in amplitude during superfusion with dopamine, explicable as a result of the drug-induced hyperpolarization. The 'off' response following the i.j.p., decreased transiently when the membrane potential was hyperpolarized to its maximum value. Then it increased to values larger than control as the membrane repolarized. Vasoactive intestinal polypeptide (VIP, 10(-6) M) produced a similar response but hyperpolarizations were smaller. 4. Of the tested catecholamines, isoprenaline, phenylephrine, butylated hydroxytoluene-920 (BHT-920) and clonidine were ineffective whereas the potency order for other catecholamines was dopamine greater than noradrenaline greater than or equal to adrenaline greater than DOPA. The catecholamine-induced responses were not affected by alpha- or beta-adrenoreceptor antagonists given alone or in combination. Of the dopamine receptor antagonists tested domperidone was without effect, whereas haloperidol reduced and bulbocapnine blocked the response. The findings suggested that a receptor resembling DA1-type peripheral receptor mediated the effects of dopamine on opossum oesophagus. 5. The catecholamine-induced responses and those to VIP disappeared completely in Cl-(-)free medium (isethionate replacement). 6. Conditioning depolarization of the smooth muscle cells decreased but hyperpolarization increased the amplitude of the hyperpolarization (up to 20 mV). With larger hyperpolarizations the responses decreased and disappeared at around 50 mV hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3625558

Kv7(KCNQ)-K+-Channels Influence Total Peripheral Resistance in Female but Not Male Rats, and Hamper Catecholamine Release in Hypertensive Rats of Both Sexes

PubMed Central

Berg, Torill

2018-01-01

K+-channels of the Kv7/KCNQ-family hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells (VSMC). Kv7 may therefore play a role in blood pressure (BP) homeostasis, and prevent a high total peripheral vascular resistance (TPR), a hallmark of hypertensive disease. The present study analyzed if Kv7 channels influence catecholamine release and TPR in normotensive (WKY) and spontaneously hypertensive rats (SHR), and if they may contribute to the antihypertensive protection seen in young, female SHR. Tyramine-stimulated norepinephrine release evokes an adrenergic cardiovascular response, and also allows modulation of release to be reflected in the overflow to plasma. The experiment itself activated some secretion of epinephrine. The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (2) Surprisingly, the Kv7-openers retigabine (Kv7.2-7.5) and ICA-27243 (Kv7.2-7.3-preferring) increased catecholamine release in female SHR. (3) The rise in TPR following tyramine-stimulated norepinephrine release was increased by XE-991 but not chromanol in the female WKY only. (4) Retigabine and ICA-27243 reduced the TPR-response to tyramine in the female SHR only. These results suggested: (1) Up-regulation of Kv7.2-7.3 function in sympathetic neurons and chromaffin cells hampered catecholamine release in SHR of both sexes. (2) The increase catecholamine release observed after channel openers in the female SHR may possibly involve reduced transmission in cholinergic neurons which hamper catecholamine release. These two mechanisms may serve to counter-act the hyperadrenergic state in SHR. (3) Kv7.4, most likely in the vasculature, opposed the tension-response to norepinephrine in the female WKY. (4) Vascular Kv7.4-7.5 could be stimulated and then opposed norepinephrine-induced vasoconstriction in the female SHR. (5) Vascular Kv7 channels did not counter-act norepinephrine induced vasoconstriction in male rats, possibly due to different Kv7 channel regulation. Kv7 channels may represent a novel target for antihypertensive therapy. PMID:29515459

Kv7(KCNQ)-K+-Channels Influence Total Peripheral Resistance in Female but Not Male Rats, and Hamper Catecholamine Release in Hypertensive Rats of Both Sexes.

PubMed

Berg, Torill

2018-01-01

K + -channels of the Kv7/KCNQ-family hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells (VSMC). Kv7 may therefore play a role in blood pressure (BP) homeostasis, and prevent a high total peripheral vascular resistance (TPR), a hallmark of hypertensive disease. The present study analyzed if Kv7 channels influence catecholamine release and TPR in normotensive (WKY) and spontaneously hypertensive rats (SHR), and if they may contribute to the antihypertensive protection seen in young, female SHR. Tyramine-stimulated norepinephrine release evokes an adrenergic cardiovascular response, and also allows modulation of release to be reflected in the overflow to plasma. The experiment itself activated some secretion of epinephrine. The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (2) Surprisingly, the Kv7-openers retigabine (Kv7.2-7.5) and ICA-27243 (Kv7.2-7.3-preferring) increased catecholamine release in female SHR. (3) The rise in TPR following tyramine-stimulated norepinephrine release was increased by XE-991 but not chromanol in the female WKY only. (4) Retigabine and ICA-27243 reduced the TPR-response to tyramine in the female SHR only. These results suggested: (1) Up-regulation of Kv7.2-7.3 function in sympathetic neurons and chromaffin cells hampered catecholamine release in SHR of both sexes. (2) The increase catecholamine release observed after channel openers in the female SHR may possibly involve reduced transmission in cholinergic neurons which hamper catecholamine release. These two mechanisms may serve to counter-act the hyperadrenergic state in SHR. (3) Kv7.4, most likely in the vasculature, opposed the tension-response to norepinephrine in the female WKY. (4) Vascular Kv7.4-7.5 could be stimulated and then opposed norepinephrine-induced vasoconstriction in the female SHR. (5) Vascular Kv7 channels did not counter-act norepinephrine induced vasoconstriction in male rats, possibly due to different Kv7 channel regulation. Kv7 channels may represent a novel target for antihypertensive therapy.

[The catecholamine content of the hypothalamus during the modelling of the ulcer process in the gastroduodenal area].

PubMed

Iemel'ianenko, I V; Sultanova, I D; Voronych, N M

1995-01-01

The content of catecholamines in rat hypothalamus in experimental ulcer process in gastroduodenal region has been studied in experiments on rats. It was determined that under these conditions the content of hypothalamus adrenalin increases and the content of noradrenalin decreases. The level of dofamin and DOFA in this brain structure changes in phases. The mentioned shifts depended on the duration and character of the pathological process in the gastroduodenal region.

Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

PubMed

Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura

2015-05-01

Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure.

PubMed

Fargali, Samira; Garcia, Angelo L; Sadahiro, Masato; Jiang, Cheng; Janssen, William G; Lin, Wei-Jye; Cogliani, Valeria; Elste, Alice; Mortillo, Steven; Cero, Cheryl; Veitenheimer, Britta; Graiani, Gallia; Pasinetti, Giulio M; Mahata, Sushil K; Osborn, John W; Huntley, George W; Phillips, Greg R; Benson, Deanna L; Bartolomucci, Alessandro; Salton, Stephen R

2014-05-01

Secretion of proteins and neurotransmitters from large dense core vesicles (LDCVs) is a highly regulated process. Adrenal LDCV formation involves the granin proteins chromogranin A (CgA) and chromogranin B (CgB); CgA- and CgB-derived peptides regulate catecholamine levels and blood pressure. We investigated function of the granin VGF (nonacronymic) in LDCV formation and the regulation of catecholamine levels and blood pressure. Expression of exogenous VGF in nonendocrine NIH 3T3 fibroblasts resulted in the formation of LDCV-like structures and depolarization-induced VGF secretion. Analysis of germline VGF-knockout mouse adrenal medulla revealed decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content and circulating plasma epinephrine, and decreased adrenal CgB. These neurochemical changes in VGF-knockout mice were associated with hypertension. Germline knock-in of human VGF1-615 into the mouse Vgf locus rescued the hypertensive knockout phenotype, while knock-in of a truncated human VGF1-524 that lacks several C-terminal peptides, including TLQP-21, resulted in a small but significant increase in systolic blood pressure compared to hVGF1-615 mice. Finally, acute and chronic administration of the VGF-derived peptide TLQP-21 to rodents decreased blood pressure. Our studies establish a role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure.

Effects of Mind-Body Training on Cytokines and Their Interactions with Catecholamines.

PubMed

Jang, Joon Hwan; Park, Hye Yoon; Lee, Ui Soon; Lee, Kyung-Jun; Kang, Do-Hyung

2017-07-01

Mind-body training (MBT) may control reactions to stress and regulate the nervous and immune systems. The present study was designed to assess the effects of MBT on plasma cytokines and their interactions with catecholamines. The study group consisted of 80 subjects who practice MBT and a control group of 62 healthy subjects. Plasma catecholamine (norepinephrine, NE; epinephrine, E; and dopamine, DA) and cytokine (TNF-alpha, IL-6, IFN-gamma, and IL-10) levels were measured, and the differences between the MBT and control groups and the interactions of cytokines with catecholamines were investigated. A significant increase in IL-10+IFN-gamma was found in females of the MBT group compared with controls. Also, a significant increase of IL-10 (anti-inflammatory cytokine) in the MBT group was shown in a specific condition in which TNF-alpha and IL-6 (pro-inflammatory cytokines) are almost absent (≤1 ng/L) compared with controls. In the MBT group, significant positive correlations were found between IL-10 and the NE/E ratio and between IL-10 and the DA/E ratio, whereas the control group did not show any such correlations. MBT may increase IL-10, under specific conditions such as a decrease of pro-inflammatory cytokines or E, which may regulate the stress response and possibly contribute to effective and beneficial interactions between the nervous and immune systems.

Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles.

PubMed

Mandela, Prashant; Chandley, Michelle; Xu, Yao-Yu; Zhu, Meng-Yang; Ordway, Gregory A

2010-01-01

Treatment of rats with reserpine, an inhibitor of the vesicular monoamine transporter (VMAT), depletes norepinephrine (NE) and regulates NE transporter (NET) expression. The present study examined the molecular mechanisms involved in regulation of the NET by reserpine using cultured cells. Exposure of rat PC12 cells to reserpine for a period as short as 5min decreased [(3)H]NE uptake capacity, an effect characterized by a robust decrease in the V(max) of the transport of [(3)H]NE. As expected, reserpine did not displace the binding of [(3)H]nisoxetine from the NET in membrane homogenates. The potency of reserpine for reducing [(3)H]NE uptake was dramatically lower in SK-N-SH cells that have reduced storage capacity for catecholamines. Reserpine had no effect on [(3)H]NE uptake in HEK-293 cells transfected with the rat NET (293-hNET), cells that lack catecholamine storage vesicles. NET regulation by reserpine was independent of trafficking of the NET from the cell surface. Pre-exposure of cells to inhibitors of several intracellular signaling cascades known to regulate the NET, including Ca(2+)/Ca(2+)-calmodulin dependent kinase and protein kinases A, C and G, did not affect the ability of reserpine to reduce [(3)H]NE uptake. Treatment of PC12 cells with the catecholamine depleting agent, alpha-methyl-p-tyrosine, increased [(3)H]NE uptake and eliminated the inhibitory effects of reserpine on [(3)H]NE uptake. Reserpine non-competitively inhibits NET activity through a Ca(2+)-independent process that requires catecholamine storage vesicles, revealing a novel pharmacological method to modify NET function. Further characterization of the molecular nature of reserpine's action could lead to the development of alternative therapeutic strategies for treating disorders known to be benefitted by treatment with traditional competitive NET inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

PubMed

Gaykema, Ronald P A; Goehler, Lisa E

2011-03-01

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from immune-sensory caudal brainstem sources target distinct populations of forebrain neurons that likely mediate different aspects of sickness. The caudal medullary catecholaminergic projections to the hypothalamus may significantly contribute to brain mechanisms that induce behavioral "fatigue" in the context of physiological stressors. Copyright © 2010 Elsevier Inc. All rights reserved.

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

PubMed Central

Gaykema, Ronald P.A.; Goehler, Lisa E.

2010-01-01

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from immune-sensory caudal brainstem sources target distinct populations of forebrain neurons that likely mediate different aspects of sickness. The caudal medullary catecholaminergic projections to the hypothalamus may significantly contribute to brain mechanisms that induce behavioral “fatigue” in the context of physiological stressors. PMID:21075199

A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites.

PubMed

Xie, Li; Chen, Liqin; Gu, Pan; Wei, Lanlan; Kang, Xuejun

2018-03-01

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and related diseases, but their precise measurement is still a challenge. Many protocols have been described for neurotransmitter measurement by a variety of instruments, including high-pressure liquid chromatography (HPLC). However, there are shortcomings, such as complicated operation or hard-to-detect multiple targets, which cannot be avoided, and presently, the dominant analysis technique is still HPLC coupled with sensitive electrochemical or fluorimetric detection, due to its high sensitivity and good selectivity. Here, a detailed protocol is described for the pretreatment and detection of catecholamines with high pressure liquid chromatography with electrochemical detection (HPLC-ECD) in real urine samples of infants, using electrospun composite nanofibers composed of polymeric crown ether with polystyrene as adsorbent, also known as the packed-fiber solid phase extraction (PFSPE) method. We show how urine samples can be easily precleaned by a nanofiber-packed solid phase column, and how the analytes in the sample can be rapidly enriched, desorbed, and detected on an ECD system. PFSPE greatly simplifies the pretreatment procedures for biological samples, allowing for decreased time, expense, and reduction of the loss of targets. Overall, this work illustrates a simple and convenient protocol for solid-phase extraction coupled to an HPLC-ECD system for simultaneous determination of three monoamine neurotransmitters (norepinephrine (NE), epinephrine (E), dopamine (DA)) and two of their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC)) in infants' urine. The established protocol was applied to assess the differences of urinary catecholamines and their metabolites between high-risk infants with perinatal brain damage and healthy controls. Comparative analysis revealed a significant difference in urinary MHPG between the two groups, indicating that the catecholamine metabolites may be an important candidate marker for early diagnosis of cases at risk for brain damage in infants.

Olive ingestion causing a false suspicion of relapsed neuroblastoma: A case of "oliveblastoma?"

PubMed

Flynn, Nick; LeFebvre, Amanda; Messahel, Boo; Hogg, Sarah L

2018-06-19

Measurement of the urine catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) are the standard method for detecting disease recurrence in neuroblastoma. We present a case of abnormal concentrations of catecholamine metabolites that prompted investigations for relapsed neuroblastoma. However, further study revealed that the abnormal biochemistry was likely due to ingestion of olives. Olive ingestion should be considered when interpreting urine HVA and VMA results, and excluded if concentrations are unexpectedly abnormal. © 2018 Wiley Periodicals, Inc.

Effects of endotoxin on monoamine metabolism in the rat.

NASA Technical Reports Server (NTRS)

Pohorecky, L. A.; Wurtman, R. J.; Taam, D.; Fine, J.

1972-01-01

Examination of effects of administered endotoxin on catecholamine metabolism in the rat brain, sympathetic neurons, and adrenal medulla. It is found that endotoxin, administered intraperitoneally, lowers the norepinephrine content in peripheral sympathetic neurons and the brain, and the catecholamine content in the adrenal medulla. It also accelerates the disappearance of H3-norepinephrine from all these tissues. It is therefore suggested that the effects of endotoxin on body temperature may be mediated in part by central non-adrenergic neurons.

An amplified chemiluminescence system based on Si-doped carbon dots for detection of catecholamines.

PubMed

Amjadi, Mohammad; Hallaj, Tooba; Manzoori, Jamshid L; Shahbazsaghir, Tahmineh

2018-08-05

We report on a chemiluminescence (CL) system based on simultaneous enhancing effect of Si-doped carbon dots (Si-CDs) and cetyltrimethylammonium bromide (CTAB) on HCO 3 - -H 2 O 2 reaction . The possible CL mechanism is investigated and discussed. Excited-state Si-CDs was found to be the final emitting species, which are probably produced via electron and hole injection by oxy-radicals. The effect of several other heteroatom-doped CDs and undoped CDs was also investigated and compared with Si-CDs. Furthermore, it was found that catecholamines such as dopamine, adrenaline and noradrenaline remarkably diminish the CL intensity of Si-CD-HCO 3 - -H 2 O 2 -CTAB system. By taking advantage of this fact, a sensitive probe was designed for determination of dopamine, adrenaline and noradrenaline with a limit of detection of 0.07, 0.60 and 0.01 μM, respectively. The method was applied to the determination of catecholamines in human plasma samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

PubMed

Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

2015-01-01

In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

[Bronchial reactivity and mucosal bioamines as criteria for acute bronchitis becoming chronic].

PubMed

Artem'eva, E G; Latfullin, I A

2002-01-01

To study bronchial reactivity and sensitivity with consideration of histamine, serotonin and catecholamines concentration in bronchial mucosa in patients with acute bronchitis (AB) as possible criteria of its becoming chronic. Before the treatment 116 patients with verified AB were examined using inhalation provocative tests (IPT) with histamine, serotonin and obsidian in increasing doses. Also, external respiration function was studied. IPT were repeated after the course of treatment. 87 of 116 AB patients exhibited high bronchial sensitivity and reactivity to inhalations of histamine, serotonin, obsidian. In parallel, there was a rise in the levels of histamine and serotonin and a fall in the level of catecholamines in bronchial mucosa (alveolar macrophages, lymphocytes, neutrophils, mast and APUD-cells). Changes in monoamines concentration in bronchial mucosa were relevant to activity of bronchial inflammation and the presence of obstructive syndrome. Persistent bronchial hyperreactivity to inhalations of histamine and obsidian along with high histamine levels and low level of catecholamines in alveolar macrophages, lymphocytes and mucus is a criterion of bronchitis transformation to chronic one.

Cardiovascular manifestations of phaeochromocytoma.

PubMed

Prejbisz, Aleksander; Lenders, Jacques W M; Eisenhofer, Graeme; Januszewicz, Andrzej

2011-11-01

Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma, such as hypertensive emergencies, result from a rapid and massive release of catecholamines from the tumour. More rarely, patients with phaeochromocytoma present with low blood pressure or even shock that may then precede multisystem crisis. Sinus tachycardia, with palpitations as the presenting symptom, is the most prevalent abnormality of cardiac rhythm in phaeochromocytoma, but tumours can also be associated with more serious ventricular arrhythmias or conduction disturbances. Reversible dilated or hypertrophic cardiomyopathy are well established cardiac manifestations of phaeochromocytoma, with more recent attention to an increasing number of cases with Takotsubo cardiomyopathy. This review provides an update on the cause, clinical presentation and treatment of the cardiovascular manifestations of phaeochromocytoma. As the cardiovascular complications of phaeochromocytoma can be life-threatening, all patients who present with manifestations that even remotely suggest excessive catecholamine secretion should be screened for the disease.

Cardiovascular effects of simulated zero-gravity in humans

NASA Astrophysics Data System (ADS)

Bonde-Petersen, F.; Suzuki, Y.; Sadámoto, T.; Juel Christensen, N.

Head-down and heat-up tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. Parameters: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relativē plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and—as a new finding—catecholamines, which were 30-50% lower compared with both + 5 and - 5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and FVR slowly decreased over 6 hr. HOWI is a stronger stimulus than - 5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.

Psychophysiological biomarkers of workplace stressors

PubMed Central

Chandola, Tarani; Heraclides, Alexandros; Kumari, Meena

2010-01-01

Workplace stressors are associated with greater coronary heart disease risk, although there is debate over the psychophysiological consequences of work stress. This study builds on recent reviews and examines the literature linking work stress with sympatho-adrenal biomarkers (plasma catecholamines and heart rate variability) and HPA axis biomarkers- the post-morning profile of cortisol. Methods Relevant studies using appropriate search terms were searched using the bibliographic databases PubMed, Embase, Biosys and Toxline. Four studies on plasma catecholamines, ten studies on heart rate variability, and sixteen studies on post-morning cortisol were reviewed. Results In the majority of studies that examined the association of HRV and work stress, greater reports of work stress is associated with lower heart rate variability. The findings for plasma catecholamines and cortisol secretion are less clear cut and suffer from poorer quality of studies in general. Conclusion There is evidence that work stress is related to elevated stress responses in terms of sympatho-adrenal and HPA axis biomarkers. PMID:19914288

Calorigenic effect of glucagon and catecholamines in king penguin chicks.

PubMed

Barre, H; Rouanet, J L

1983-06-01

The calorigenic action of glucagon and catecholamine infusion was evaluated in winter-acclimatized king penguin chicks at 20 and 0 degrees C ambient temperature (Ta). At Ta = 20 degrees C the mean increase in metabolic rate was 0.73 W . kg-1 for epinephrine (80 micrograms . kg-1), 0.42 W . kg-1 for norepinephrine (150 micrograms . kg-1), and 1.16 W . kg-1 for glucagon (0.75 micrograms . kg-1); i.e., respectively 30, 17, and 47% of the control value. The maximum response to glucagon reached 89% over control. At Ta = 0 degrees C, for the same glucagon infusion, the mean increase in specific metabolic rate was 0.84 W . kg-1, 27% of control rate. In the cold, glucagon infusion inhibited shivering and substituted its calorigenic action, resulting in a less apparent effect. In contrast with the negligible effect of catecholamines, glucagon infused at low doses exerted a powerful calorigenic action in young king penguins and could be considered as a possible nonshivering thermogenesis mediator.

ADHD impacted by sulfotransferase (SULT1A) inhibition from artificial food colors and plant-based foods.

PubMed

Eagle, Ken

2014-08-01

Five recent reviews have analyzed trials on the association between artificial food colors and ADHD; the 50 underlying studies and the reviews in aggregate were inconclusive. Recent work has shown human in vivo SULT1A inhibition leading to incremental catecholamines, and an inverted-U relationship between brain catecholamines and proper functioning of the prefrontal cortex where ADHD behavior can arise. This study re-examined the same underlying trials for evidence that SULT1A inhibitors were in the placebos and other inactive foods, that these "inactive" materials were symptomatic, and that ADHD symptoms exhibited an inverted-U response to SULT1A inhibition. Nearly all the underlying diets, and many placebos and delivery vehicles, were found to contain SULT1A inhibitors. Eight publications provided evidence of ADHD symptoms caused by the "inactive" materials containing SULT1A inhibitors. Ten studies showed additional SULT1A inhibitors reducing the symptoms of some subjects. SULT1A inhibitors in foods, including natural substances and artificial food colors, have a role in ADHD that can both worsen or improve symptoms. Mechanistically, SULT1A enzymes normally deactivate catecholamines, especially dopamine formed in the intestines; SULT1A inhibition can influence brain catecholamines through the intermediary of plasma tyrosine levels, which are influenced by dopamine inhibition of intestinal tyrosine hydroxylase. Biochemical measurements focused on SULT1A activity and plasma tyrosine concentrations are proposed for future work. Copyright © 2014 Elsevier Inc. All rights reserved.

Catecholamime Interactions with the Cardiac Ryanodine Receptor

NASA Astrophysics Data System (ADS)

Klipp, Robert Carl

The cardiac ryanodine receptor (RyR2) is a Ca2+ ion channel found in the sarcoplasmic reticulum (SR), an intracellular membranous Ca2+ storage system. It is well known that a destabilization of RyR2 can lead to a Ca2+ flux out of the SR, which results in an overload of intracellular Ca2+; this can also lead to arrhythmias and heart failure. The catecholamines play a large role in the regulation of RyR2; stimulation of the beta-adrenergic receptor on the cell membrane can lead to a hyperphosphorylation of RyR2, making it more leaky to Ca2+. We have previously shown that strong electron donors will inhibit RyR2. It is hypothesized that the catecholamines, sharing a similar structure with other proven inhibitors of RyR2, will also inhibit RyR2. Here we confirm this hypothesis and show for the first time that the catecholamines, isoproterenol and epinephrine, act as strong electron donors and inhibit RyR2 activity at the single channel level. This data suggests that the catecholamines can influence RyR2 activity at two levels. This offers promising insight into the potential development of a new class of drugs to treat heart failure and arrhythmia; ones that can both prevent the hyperphosphorylation of RyR2 by blocking the beta-adrenergic receptor, but can also directly inhibit the release of Ca2+ from RyR2.

The catecholamine response to spaceflight: role of diet and gender.

PubMed

Stein, T P; Wade, C E

2001-09-01

Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

Nicotine promotes cell proliferation via {alpha}7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee

Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a {beta}{sub 1}- and {beta}{sub 2}-selective antagonist, respectively, suggesting the role of {beta}-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-{beta}-hydroxylase (D{beta}H) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferationmore » and adrenaline production. Expression of {alpha}7-nicotinic acetylcholine receptor ({alpha}7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an {alpha}7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and D{beta}H expression as well as adrenaline production. Taken together, through the action on {alpha}7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and {beta}-adrenergic activation. These data reveal the contributory role {alpha}7-nAChR and {beta}-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer.« less

Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

PubMed

Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

2008-09-01

Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

Calcium-dependent transferrin receptor recycling in bovine chromaffin cells.

PubMed

Knight, Derek E

2002-04-01

The release of regulated secretory granules is known to be calcium dependent. To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined. Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min. Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar. The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool. Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different. The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively. There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled. Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion. These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion.

Analysis of catecholamines in urine by unique LC/MS suitable ion-pairing chromatography.

PubMed

Bergmann, Marianne L; Sadjadi, Seyed; Schmedes, Anne

2017-07-01

The catecholamines, epinephrine (E) and norepinephrine (NE) are small polar, hydrophilic molecules, posing significant challenges to liquid chromatography - tandem mass spectrometry (LC-MS/MS) method development. Specifically, these compounds show little retention on conventional reversed-phase liquid chromatography columns. This work presents development and validation of an LC-MS/MS method for determining catecholamines in urine, based on a new approach to ion-pairing chromatography (IPC), in which the ion-pairing reagent (IPR), 1-Heptane Sulfonic Acid (HSA), is added to the extracted samples instead of the mobile phases. A Hamilton STARlet workstation carried out the solid phase extraction of urine samples. The extracted samples were diluted with 60mmol/L HSA and injected on a Kinetex core-shell biphenyl column with conventional LC-MS/MS suitable mobile phases. Chromatographic separation of E and NE was achieved successfully with very stable retention times (RT). In 484 injections, the RTs were steady with a CV of less than ±4%. Furthermore, HSA was separated from E and NE, allowing HSA to be diverted to waste instead of entering the mass spectrometer ion chamber. The method was validated with good analytical performance, and even though the analysis for urinary catecholamines is increasingly being replaced by plasma free metanephrines in diagnosing pheochromocytomas, this work represents the application of a new analytical technique that can be transferred to other small polar molecules, that are difficult to chromatograph on traditional reversed phase columns. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

PubMed

Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

2017-09-01

The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

[Phaeochromocytoma revealed by a cardiogenic shock treated by extracorporeal life support].

PubMed

Contargyris, C; Nee, L; Saby, C; Kerbaul, F; Peytel, E

2012-12-01

Phaeochromocytoma is a catecholamine-secreting tumour that originates from the chromaffin cells in the adrenal medulla in 85% of the cases. Phaeochromocytoma typically presents with the classic signs and symptoms of paroxysmal hypertension, tachycardia, and episodic headache in young adults. However, it rarely may manifest as cardiogenic shock due to a catecholamine induced cardiomyopathy. We report the use of central extracorporeal life support (ECLS) in a young man admitted to our department because of cardiogenic shock caused by phaeochromocytoma. Copyright © 2012. Published by Elsevier SAS.

Catecholamines of the adrenal medula and their morphological changes during adaptation to repeated immobilization stress

NASA Technical Reports Server (NTRS)

Kvetnansky, R.; Mitro, A.; Mikulaj, L.; Hocman, G.

1980-01-01

Changes of the adrenal medulla of rats were studied in the course of adaptation to repeated immobilization stress. An increase in the number of cells in the adrenal medulla was found in the adapted animals; this increase was confirmed by weight indices of the medulla and by cell counts per surface unit. Simultaneous karyometric measurements of the nuclei of adrenal medulla cells and an analysis of the catecholamine contents in the adrenals explain the increased activity of the adrenal medulla in the course of adaptation.

Hypertensive crisis during wide excision of gastrointestinal stromal cell tumor (GIST): Undiagnosed paraganglioma -A case report-.

PubMed

Shinn, Helen Ki; Jung, Jong Kwon; Park, Jay Kim; Kim, Jong Hoon; Jung, In Young; Lee, Hong Sik

2012-03-01

Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause severe hypertensive crisis during anesthesia or surgery if undiagnosed preoperatively. Extraluminal perigastric masses may be presumed to be gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when histologic confirmation is not possible. Therefore, without a histologic diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken for GIST. We report a case of preoperatively undiagnosed PGL which caused hypertensive crisis during anesthesia for retroperitoneal mass excision.

Imidacloprid, a neonicotinoid insecticide, facilitates tyrosine hydroxylase transcription and phenylethanolamine N-methyltransferase mRNA expression to enhance catecholamine synthesis and its nicotine-evoked elevation in PC12D cells.

PubMed

Kawahata, Ichiro; Yamakuni, Tohru

2018-02-01

Imidacloprid is a neonicotinoid insecticide acting as an agonist of nicotinic acetylcholine receptors (nAChRs) in the target insects. However, questions about the safety to mammals, including human have emerged. Overactivation of mammalian peripheral catecholaminergic systems leads to onset of tachycardia, hypertension, vomiting, etc., which have been observed in acutely imidacloprid-poisoned patients as well. Physiological activation of the nAChRs is known to drive catecholamine biosynthesis and secretion in mammalian adrenal chromaffin cells. Yet, the impacts of imidacloprid on the catecholaminergic function of the chromaffin cells remain to be evaluated. In this study using PC12D cells, a catecholaminergic cell line derived from the medulla chromaffin-cell tumors of rat adrenal gland, we examined whether imidacloprid itself could impact the catecholamine-synthesizing ability. Imidacloprid alone did facilitate tyrosine hydroxylase (TH) transcription via activation of α3β4 nAChR and the α7 subunit-comprising receptor. The insecticide showed the TH transcription-facilitating ability at the concentrations of 3 and 30 μM, at which acetylcholine is known to produce physiological responses, including catecholamine secretion through the nAChRs in adrenal chromaffin cells. The insecticide-facilitated TH transcription was also dependent on PKA- and RhoA-mediated signaling pathways. The insecticide coincidentally raised levels of TH and phenylethanolamine N-methyltransferase (PNMT) mRNA, and as a consequence, increased catecholamine production, although the efficacy of the neonicotinoid was lesser than that of nicotine, indicating its partial agonist-like action. Intriguingly, in cultured rat adrenal chromaffin cells, imidacloprid did increase levels of TH and PNMT protein. When the chromaffin cells were treated with nicotine in the presence of the insecticide, nicotine-elevated adrenaline production was enhanced due to facilitation of nicotine-increased TH and PNMT protein expression, and simultaneous enhancement of nicotine-elevated adrenaline secretion also took place. These findings thus suggest that imidacloprid may facilitate the physiological functions of adrenal glands in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice

PubMed Central

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

2014-01-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. PMID:23499051

Sex-related differences in fuel utilization and hormonal response to exercise: implications for individuals with type 1 diabetes.

PubMed

Brockman, Nicole K; Yardley, Jane E

2018-06-01

Sex-related differences in metabolic and neuroendocrine response to exercise in individuals without diabetes have been well established. Men and women differ in fuel selection during exercise, in which women rely to a greater extent on fat oxidation, whereas males rely mostly on carbohydrate oxidation for energy production. The difference in fuel selection appears to be mediated by sex-related differences in hormonal (including catecholamines, growth hormone, and estrogen) response to different types and intensities of exercise. In general, men exhibit an amplified counter-regulatory response to exercise, with elevated levels of catecholamines compared with women. However, women exhibit greater sensitivity to the lipolytic action of the catecholamines and deplete less of their glycogen stores than men during exercise, which suggests that women may experience a greater defense in blood glucose control after exercise than men. Conversely, little is known about sex-related differences in response to exercise in individuals with type 1 diabetes (T1D). A single study investigating sex-related differences in response to moderate aerobic exercise in individuals with T1D found sex-related differences in catecholamine response and fuel selection, but changes in blood glucose were not measured. To our knowledge, there are no studies investigating sex-related differences in blood glucose responses to different types and intensities of exercise in individuals with T1D. This review summarizes sex-related differences in exercise responses that could potentially impact blood glucose levels during exercise in individuals with T1D and highlights the need for further research.

The catecholamine response to spaceflight: role of diet and gender

NASA Technical Reports Server (NTRS)

Stein, T. P.; Wade, C. E.

2001-01-01

Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

PubMed Central

Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

2007-01-01

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8μg 100 g−1 day−1, s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases. PMID:17218354

Changes in Body Mass Index in Pheochromocytoma Patients Following Adrenalectomy.

PubMed

Spyroglou, Ariadni; Adolf, Christian; Hahner, Stefanie; Quinkler, Marcus; Ladurner, Roland; Reincke, Martin; Beuschlein, Felix

2017-03-01

Catecholamine excess from pheochromocytoma results in cardiovascular symptoms such as arterial hypertension and tachycardia and induces metabolic alterations including glucose intolerance and increase in resting metabolic rate. The objective of our study was to investigate the effect of surgical cure of pheochromocytoma on body-mass-index and the correlation of body-mass-index changes to preoperative endocrine parameters. Pheochromocytoma patients from the Munich ENSAT Registry were matched (1:2) for age and gender to patients from the German Conn's Registry, who had undergone surgery for aldosterone-producing-adenomas. Thereby, 43 pheochromocytoma patients (17 males/26 females) and 86 aldosterone-producing-adenoma patients were analyzed for body-mass-index, blood pressure, and catecholamine levels before and one year after adrenalectomy. Seventy-four percent of pheochromocytoma patients were hypertensive preoperatively and 48% one year postoperatively. Systolic blood pressure did not differ significantly in pre- and postoperative measurements whereas diastolic blood pressure was significantly reduced over time. Moreover, pheochromocytoma patients gained body weight (p<0.001) one year following adrenalectomy accompanied by significant increases in body-mass-index, whereas aldosterone-producing adenoma patients displayed a slight weight loss. Despite weight gain, diagnosis of diabetes mellitus dropped from 9 of 43 investigated pheochromocytoma patients at baseline to 4 at follow-up. A significant correlation between body-mass-index changes to the preoperative catecholamine levels was found only for urinary normetanephrines. These data suggest that normalization of chronic catecholamine excess by adrenalectomy is associated with an increase in body-mass-index, which is more pronounced in patients with high preoperative levels of urinary normetanephrines. © Georg Thieme Verlag KG Stuttgart · New York.

Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla

PubMed Central

Schneider, Allan S.; Herz, Ruth; Rosenheck, Kurt

1977-01-01

Bovine adrenal chromaffin cells were isolated by removal of the cortex and sequential collagenase digestion of the medulla. The catecholamine secretory function of these cells was characterized with respect to acetylcholine stimulation, cation requirements, and cytoskeletal elements. The dose-response curve for stimulated release had its half-maximum value at 10-5 M acetylcholine, and maximum secretion was on the average 7 times that of control basal secretion. The differential release of epinephrine versus norepinephrine after stimulation with 0.1 mM acetylcholine occurred in proportion to their distribution in the cell suspension. The cholinergic receptors were found to be predominantly nicotinic. The kinetics of catecholamine release were rapid, with significant secretion occurring in less than 60 sec and 85% of maximum secretion within 5 min. A critical requirement for calcium in the extracellular medium was demonstrated, and 80% of maximum secretion was achieved at physiologic calcium concentrations. Stimulation by excess potassium (65 mM KCl) also induced catecholamine secretion which differed from acetylcholine stimulation in being less potent, in having a different dependence on calcium concentration, and in its response to the local anesthetic tetracaine. Tetracaine, which is thought to inhibit membrane cation permeability, was able to block acetylcholine-stimulated but not KCl-stimulated secretion. The microtubule disrupting agent vinblastine was able to block catecholamine release whereas the microfilament disrupter cytochalasin B had little effect. The results show the isolated bovine chromaffin cells to be viable, functioning, and available in large quantity. These cells now provide an excellent system for studying cell surface regulation of hormone and neurotransmitter release. PMID:270738

Effect of norepinephrine on swelling-induced potassium transport in duck red cells. Evidence against a volume-regulatory decrease under physiological conditions

PubMed Central

1985-01-01

Duck red cells exhibit specific volume-sensitive ion transport processes that are inhibited by furosemide, but not by ouabain. Swelling cells in a hypotonic synthetic medium activates a chloride- dependent, but sodium-independent, potassium transport. Shrinking cells in a hypertonic synthetic medium stimulates an electrically neutral co- transport of [Na + K + 2 Cl] with an associated 1:1 K/K (or K/Rb) exchange. These shrinkage-induced modes can also be activated in both hypo- and hypertonic solutions by beta-adrenergic catecholamines (e.g., norepinephrine). Freshly drawn cells spontaneously shrink approximately 4-5% when removed from the influence of endogenous plasma catecholamines, either by incubation in a catecholamine-free, plasma- like synthetic medium, or in plasma to which a beta-receptor blocking dose of propranolol has been added. This spontaneous shrinkage resembles the response of hypotonically swollen cells in that it is due to a net loss of KCl with no change in cell sodium. Norepinephrine abolishes the net potassium transport seen in both fresh and hypotonically swollen cells. Moreover, cells swollen in diluted plasma, at physiological pH and extracellular potassium, show no net loss of KCl and water ("volume-regulatory decrease") unless propranolol is added. Examination of the individual cation fluxes in the presence of catecholamines demonstrates that activation of [Na + K + 2Cl] co- transport with its associated K/Rb exchange prevents, or overrides, swelling-induced [K + Cl] co-transport. These results, therefore, cast doubt on whether the swelling-induced [K + Cl] system can serve a volume-regulatory function under in vivo conditions. PMID:3998706

IR, UV-Vis, magnetic and thermal characterization of chelates of some catecholamines and 4-aminoantipyrine with Fe(III) and Cu(II)

NASA Astrophysics Data System (ADS)

Mohamed, Gehad G.; Zayed, M. A.; El-Dien, F. A. Nour; El-Nahas, Reham G.

2004-07-01

The dopamine derivatives participate in the regulation of wide variety of physiological functions in the human body and in medication life. Increase and/or decrease in the concentration of dopamine in human body reflect an indication for diseases such as Schizophrenia and/or Parkinson diseases. α-Methyldopa (α-MD) in tablets is used in medication of hypertension. The Fe(III) and Cu(II) chelates with coupled products of adrenaline hydrogen tartarate (AHT), levodopa (LD), α-MD and carbidopa (CD) with 4-aminoantipyrine (4-AAP) are prepared and characterized. Different physico-chemical methods like IR, magnetic and UV-Vis spectra are used to investigate the structure of these chelates. Fe(III) form 1:2 (M:catecholamines) chelates while Cu(II) form 1:1 chelates. Catecholamines behave as a bidentate mono- or dibasic ligands in binding to the metal ions. IR spectra show that the catecholamines are coordinated to the metal ions in a bidentate manner with O,O donor sites of the phenolic - OH. Magnetic moment measurements reveal the presence of Fe(III) chelates in octahedral geometry while the Cu(II) chelates are square planar. The thermal decomposition of Fe(III) and Cu(II) complexes is studied using thermogravimetric (TGA) and differential thermal analysis (DTA) techniques. The water molecules are removed in the first step followed immediately by decomposition of the ligand molecules. The activation thermodynamic parameters, such as, energy of activation, enthalpy, entropy and free energy change of the complexes are evaluated and the relative thermal stability of the complexes are discussed.

Adipocyte Browning and Higher Mitochondrial Function in Periadrenal But Not SC Fat in Pheochromocytoma.

PubMed

Vergnes, Laurent; Davies, Graeme R; Lin, Jason Y; Yeh, Michael W; Livhits, Masha J; Harari, Avital; Symonds, Michael E; Sacks, Harold S; Reue, Karen

2016-11-01

Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors. To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME, and SC fat depots in human adult pheo patients. This was an observational cohort study. The study took place in a university hospital. We studied 46 patients who underwent surgery for benign adrenal tumors (21 pheos and 25 controls with adrenocortical adenomas). We characterized adipocyte browning in pADR, SC, and OME fat depots for histological and immunohistological features, mitochondrial respiration rate, and gene expression. We also determined circulating levels of catecholamines and other browning-related hormones. Eleven of 21 pheo pADR adipose samples, but only one of 25 pADR samples from control patients exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised uncoupling protein 1. Mitochondria from multilocular pADR fat of pheo patients exhibited increased rates of coupled and uncoupled respiration. Global gene expression analysis in pADR fat revealed enrichment in β-oxidation genes in pheo patients with multilocular adipocytes. No SC or OME fat depots exhibited aspects of browning. Browning of the pADR depot occurred in half of pheo patients and was associated with increased catecholamines and mitochondrial activity. No browning was detected in other fat depots, suggesting that other factors are required to promote browning in these depots.

EGR-1 Expression in Catecholamine-synthesizing Neurons Reflects Auditory Learning and Correlates with Responses in Auditory Processing Areas.

PubMed

Dai, Jennifer B; Chen, Yining; Sakata, Jon T

2018-05-21

Distinguishing between familiar and unfamiliar individuals is an important task that shapes the expression of social behavior. As such, identifying the neural populations involved in processing and learning the sensory attributes of individuals is important for understanding mechanisms of behavior. Catecholamine-synthesizing neurons have been implicated in sensory processing, but relatively little is known about their contribution to auditory learning and processing across various vertebrate taxa. Here we investigated the extent to which immediate early gene expression in catecholaminergic circuitry reflects information about the familiarity of social signals and predicts immediate early gene expression in sensory processing areas in songbirds. We found that male zebra finches readily learned to differentiate between familiar and unfamiliar acoustic signals ('songs') and that playback of familiar songs led to fewer catecholaminergic neurons in the locus coeruleus (but not in the ventral tegmental area, substantia nigra, or periaqueductal gray) expressing the immediate early gene, EGR-1, than playback of unfamiliar songs. The pattern of EGR-1 expression in the locus coeruleus was similar to that observed in two auditory processing areas implicated in auditory learning and memory, namely the caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting a contribution of catecholamines to sensory processing. Consistent with this, the pattern of catecholaminergic innervation onto auditory neurons co-varied with the degree to which song playback affected the relative intensity of EGR-1 expression. Together, our data support the contention that catecholamines like norepinephrine contribute to social recognition and the processing of social information. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Metabologenomics of Phaeochromocytoma and Paraganglioma: An Integrated Approach for Personalised Biochemical and Genetic Testing

PubMed Central

Eisenhofer, Graeme; Klink, Barbara; Richter, Susan; Lenders, Jacques WM; Robledo, Mercedes

2017-01-01

The tremendous advances over the past two decades in both clinical genetics and biochemical testing of chromaffin cell tumours have led to new considerations about how these aspects of laboratory medicine can be integrated to improve diagnosis and management of affected patients. With germline mutations in 15 genes now identified to be responsible for over a third of all cases of phaeochromocytomas and paragangliomas, these tumours are recognised to have one of the richest hereditary backgrounds among all neoplasms. Depending on the mutation, tumours show distinct differences in metabolic pathways that relate to or even directly impact clinical presentation. At the same time, there has been improved understanding about how catecholamines are synthesised, stored, secreted and metabolised by chromaffin cell tumours. Although the tumours may not always secrete catecholamines it has become clear that almost all continuously produce and metabolise catecholamines. This has not only fuelled changes in laboratory medicine, but has also assisted in recognition of genotype-biochemical phenotype relationships important for diagnostics and clinical care. In particular, differences in catecholamine and energy pathway metabolomes can guide genetic testing, assist with test interpretation and provide predictions about the nature, behaviour and imaging characteristics of the tumours. Conversely, results of genetic testing are important for guiding how routine biochemical testing should be employed and interpreted in surveillance programmes for at-risk patients. In these ways there are emerging needs for modern laboratory medicine to seamlessly integrate biochemical and genetic testing into the diagnosis and management of patients with chromaffin cell tumours. PMID:29332973

Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

PubMed

Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

2009-01-01

The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness.

PubMed

Arnsten, Amy F T

2007-09-01

Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.

ROLE OF NEUROTRANSMITTERS AND PROTEIN SYNTHESIS IN SHORT- AND LONG-TERM MEMORY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, E.L.; Rosenzweig, M.R.; Flood, J.F.

1978-10-01

Anisomycin is an effective inhibitor of cerebral protein synthesis in mice and is also an effective amnestic agent for both passive and active behavioral tasks. From use of anisomycin in combination with a variety of stimulant and depressant drugs, we conclude that the level of arousal following acquisition plays an important role in determining the duration and the rate of the biosynthetic phase of memory formation. While we have interpreted the experiments with anisomycin as evidence for an essential role of protein in memory storage, others have suggested that side effects of inhibitors of protein synthesis on catecholamine metabolism aremore » the main cause of amnesia. Several experiments were therefore done to compare the effects of anisemycin and catecholamine inhibitors on memory. We conclude that anisomycin's principal amnestic mechanism does not involve inhibition of the catecholamine system. The results strengthen our conclusion that protein synthesis is an essential component for longterm memory trace formation. Also, it is suggested that proteins synthesized in the neuronal cell body are used, in conjunction with other molecules, to produce permanent and semi-permanent anatomical changes.« less

Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

PubMed Central

Bhagat, B.

1969-01-01

1. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H-noradrenaline 1 hr after its intravenous administration. 2. Twenty-four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. 3. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α-methyl-tyrosine showed that cardiac synthesis of noradrenaline increased about four-fold after demedullation and about three-fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. 4. There was no change in catechol-o-methyl-transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. 5. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones. PMID:5360339

Behavioral and cognitive effects of tyrosine intake in healthy human adults.

PubMed

Hase, Adrian; Jung, Sophie E; aan het Rot, Marije

2015-06-01

The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence catecholamine-related psychological functioning. We conducted a systematic review to examine the effects of tyrosine on behavior and cognition. Fifteen studies were reviewed. All studies except one involved tyrosine loading during a single test session. In most behavioral studies, there were no significant effects of tyrosine on exercise performance. In contrast, cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions. For future research we recommend moving from studying the acute effects of a single tyrosine load in small samples to studying the behavioral and cognitive effects of tyrosine in larger groups over multiple weeks. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

1988-01-01

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells.

PubMed Central

Kuijpers, G A; Vergara, L A; Calvo, S; Yadid, G

1994-01-01

1. Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration-dependent (1-100 microM) manner. At 10 microM nicotine, the IC50 value for strychnine is approximately 30 microM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3. Strychnine competes with nicotine in its effect, but not modify the apparent positive cooperatively of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release. 4. These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. PMID:7834198

Pheochromocytoma/Paraganglioma: A Poster Child for Cancer Metabolism.

PubMed

Tevosian, Sergei G; Ghayee, Hans K

2018-05-01

Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize; there are no known cures for metastasized PGLs. Original articles and reviews indexed in PubMed were identified by querying with specific PCC/PGL- and Krebs cycle pathway-related terms. Additional references were selected through the in-depth analysis of the relevant publications. We primarily discuss Krebs cycle mutations that can be instrumental in helping investigators identify key biological pathways and molecules that may serve as biomarkers of or treatment targets for PCC/PGL. The mainstay of treatment of patients with PCC/PGLs is surgical. However, the tide may be turning with the discovery of new genes associated with PCC/PGLs that may shed light on oncometabolites used by these tumors.

Ambulatory stress monitoring with a wearable bluetooth electrocardiographic device.

PubMed

Hong, Sungyoup; Yang, Youngmo; Lee, Jangyoung; Yang, Heebum; Park, Kyungnam; Lee, Suyeul; Lee, Inbum; Jang, Yongwon

2010-01-01

We tried to monitor stress by using a wearable one channel ECG device that can send ECG signals through Bluetooth wireless communication. Noxious physical and mental arithmetic stress was given three times repeatedly to healthy adults, and cortisol and catecholamines were measured serially from peripheral blood. At the same time, time domain and frequency domain parameters of heart rate variability (HRV) were calculated by taking precordial electrocardiogram. The intensity of correlation between subjective visual analogue scale (VAS) and catecholamine, cortisol, and HRV parameters according to stress was analyzed by using concordance correlation coefficients. The HRV triangular index and LF/HF ratio had high concordance correlation with the degree of stress in the physical stress model. In mental arithmetic stress model, the HRV triangular index and LF/HF ratio had weak concordance correlation with the degree of stress, and it had lower predictability than epinephrine. In both models, cortisol had some correlation with catecholamine, but it had little correlation with HRV parameters. HRV parameters using wearable one channel ECG device can be useful in predicting acute stress and also in many other areas.

Transient shock and myocardial impairment caused by phaeochromocytoma crisis.

PubMed Central

Shaw, T R; Rafferty, P; Tait, G W

1987-01-01

A patient admitted to hospital after injury to the abdomen was found to have transient hypertension which was followed by profound hypotension. ST elevation developed and extensive myocardial akinesia was seen at echocardiography, but coronary angiograms at this stage were normal. After treatment with intravenous fluids and dopamine he progressively recovered normal cardiac function. A partly necrotic catecholamine secreting tumour was later removed from the abdomen and it is likely that a kick to the abdomen had damaged the tumour and the consequent release of catecholamine had triggered a phaeochromocytoma crisis. Images Fig 1 Fig 2 PMID:3814455

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moroz, B.B.; Grozdov, S.P.; Petrovnina, E.N.

A considerable amopunt of catecholamine oxidation products, and in some cases adrenaline, were found in the blood of rabbits exposed to 800 r of x radiation. A high concentration of adrenaline was observed in the left ventricle during the first hours after exposure and during the acute period. Intravenous injection of 0.2 mg of adrenaline resulted in a strong increase in oxidation products. Injections of ephedrine did not eliminate adrenaline oxidation in irradiated rabbits, wile additions of ascorbic acid restored the oxidation products. The experiments confirmed that catecholamine oxidation follows a chinoidal type oxidation and that the oxidation products aremore » of reverse oxidation« less

[Activity of the sympatho-adrenal system in patients with hysterical psychopathy and psychasthenia].

PubMed

Trunova, M M

1978-01-01

The paper is concerned with studies of the sympathoadrenal system activity by the indices of urine excretion of catecholamine and dofa in patients with hysterical and psychasthenic psychopathy. The disorders inherent in each of the groups are demonstrated. The patients with hysterical psychopathy show an exhaustion of all links in the catecholamine metabolism, while the patients with psychasthenical psychopathy an exhaustion of the noradrenaline link. In attempting to explain the mechanisms of disturbed activity in the sympathoadrenal system in both groups the role of the functional state of nonspecific activizing brain systems was taken into consideration.

[Hypertension, catecholamine hypersecretion and potential for metastasis: recent progress in the pathophysiology and genetics of pheochromocytoma and paraganglioma].

PubMed

Plouin, Pierre-François; Amar, Laurence; Gimenez-Roqueplo, Anne-paule

2015-01-01

Pheochromocytomas and paragangliomas are catecholamine-secreting tumors usually associated with arterial hypertension. They can contribute to acute cardiovascular events. Ten to 15 percent of tumors are metastatic. Autosomal dominant gene alterations are present in more than a third of cases. The secretory phenotype and the risk of malignancy are driven by the presence of gene mutations, specifically in the subunits of succinate dehydrogenase. Recent advances in genomics have clinical implications for family screening, biological follow-up, prediction of the risk of recurrence, and therapeutic options in cases with malignant recurrence.

Studies on brain biogenic amines in methanolic extract of Cuscuta reflexa Roxb. and Corchorus olitorius Linn. seed treated mice.

PubMed

Gupta, Malaya; Mazumder, Upal Kanti; Pal, Dilipkumar; Bhattacharya, Shiladitya; Chakrabarty, Sumit

2003-01-01

The methanolic extract of both Cuscuta reflexa stem and Corchorus olitorius seed showed marked protection against convulsion induced by chemoconvulsive agents in mice. The catecholamines contained were significantly increased in the processed extract treated mice. The amount of GABA, which is most likely to be involved in seizure activity, was increased significantly in mice brain after a six week treatment. Results of the present study revealed that both the processed extracts showed a significant anticonvulsive property by altering the level of catecholamines and brain amino acids in mice.

Hypertensive crisis during wide excision of gastrointestinal stromal cell tumor (GIST): Undiagnosed paraganglioma -A case report-

PubMed Central

Shinn, Helen Ki; Jung, Jong Kwon; Park, Jay Kim; Kim, Jong Hoon; Jung, In Young

2012-01-01

Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause severe hypertensive crisis during anesthesia or surgery if undiagnosed preoperatively. Extraluminal perigastric masses may be presumed to be gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when histologic confirmation is not possible. Therefore, without a histologic diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken for GIST. We report a case of preoperatively undiagnosed PGL which caused hypertensive crisis during anesthesia for retroperitoneal mass excision. PMID:22474560

The effect of adaptive servo-ventilation on dyspnoea, haemodynamic parameters and plasma catecholamine concentrations in acute cardiogenic pulmonary oedema.

PubMed

Nakano, Shintaro; Kasai, Takatoshi; Tanno, Jun; Sugi, Keiki; Sekine, Yasumasa; Muramatsu, Toshihiro; Senbonmatsu, Takaaki; Nishimura, Shigeyuki

2015-08-01

Adaptive servo-ventilation has a potential sympathoinhibitory effect in acute cardiogenic pulmonary oedema (ACPO). To evaluate the acute effects of adaptive servo-ventilation in patients with ACPO. Fifty-eight consecutive patients with ACPO were divided into those who underwent adaptive servo-ventilation and those who received oxygen therapy alone as part of their immediate care. Visual analogue scale, vital signs, blood gas data and plasma catecholamine concentrations at baseline and 1 h during emergency care, and subsequent clinical events (death within 30 days, intubation within seven days or between seven and 30 days, and length of hospital stay) were assessed. Pre-matched and post-propensity score (PS)-matched datasets were analysed. During the first hour of adaptive servo-ventilation, plasma catecholamine concentrations fell significantly (baseline versus 1 h: epinephrine p = 0.003, norepinephrine p < 0.001, dopamine p < 0.001), with falls in blood pressure, heart rate, respiratory rate and pCO2, and rise in HCO3 and pH. In the PS-matched model, visual analogue scale (p = 0.036), systolic blood pressure (from 153.8 ± 30.7 to 133.1 ± 16.3 mmHg; p = 0.025) and plasma dopamine concentration (p = 0.034) fell significantly in the adaptive servo-ventilation group compared with the oxygen therapy alone group. The clinical outcomes between the groups were comparable. In patients with ACPO, emergency care using adaptive servo-ventilation attenuated plasma catecholamine concentrations and led to the improvement of dyspnoea, vital signs and acid-base balance, without adversely influencing clinical outcomes. Using adaptive servo-ventilation, rather than standard oxygen alone, may relieve dyspnoea and improve haemodynamic status, possibly by modulating sympathetic nerve activity. © The European Society of Cardiology 2014.

Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

PubMed

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

2013-04-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

PubMed

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

PubMed Central

King, T. Luise; Ruyle, Brian C.; Kline, David D.; Heesch, Cheryl M.

2015-01-01

Brainstem catecholamine neurons modulate sensory information and participate in control of cardiorespiratory function. These neurons have multiple projections, including to the paraventricular nucleus (PVN), which contributes to cardiorespiratory and neuroendocrine responses to hypoxia. We have shown that PVN-projecting catecholaminergic neurons are activated by hypoxia, but the function of these neurons is not known. To test the hypothesis that PVN-projecting catecholamine neurons participate in responses to respiratory challenges, we injected IgG saporin (control; n = 6) or anti-dopamine β-hydroxylase saporin (DSAP; n = 6) into the PVN to retrogradely lesion catecholamine neurons projecting to the PVN. After 2 wk, respiratory measurements (plethysmography) were made in awake rats during normoxia, increasing intensities of hypoxia (12, 10, and 8% O2) and hypercapnia (5% CO2-95% O2). DSAP decreased the number of tyrosine hydroxylase-immunoreactive terminals in PVN and cells counted in ventrolateral medulla (VLM; −37%) and nucleus tractus solitarii (nTS; −36%). DSAP produced a small but significant decrease in respiratory rate at baseline (during normoxia) and at all intensities of hypoxia. Tidal volume and minute ventilation (VE) index also were impaired at higher hypoxic intensities (10-8% O2; e.g., VE at 8% O2: IgG = 181 ± 22, DSAP = 91 ± 4 arbitrary units). Depressed ventilation in DSAP rats was associated with significantly lower arterial O2 saturation at all hypoxic intensities. PVN DSAP also reduced ventilatory responses to 5% CO2 (VE: IgG = 176 ± 21 and DSAP = 84 ± 5 arbitrary units). Data indicate that catecholamine neurons projecting to the PVN are important for peripheral and central chemoreflex respiratory responses and for maintenance of arterial oxygen levels during hypoxic stimuli. PMID:26157062

Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

PubMed

Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

2007-10-01

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

PubMed

Rocca, A; Pignat, J-M; Berney, L; Jöhr, J; Van de Ville, D; Daniel, R T; Levivier, M; Hirt, L; Luft, A R; Grouzmann, E; Diserens, K

2016-09-13

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered.

Systematic Morphometry of Catecholamine Nuclei in the Brainstem.

PubMed

Bucci, Domenico; Busceti, Carla L; Calierno, Maria T; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

2017-01-01

Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.

Systematic Morphometry of Catecholamine Nuclei in the Brainstem

PubMed Central

Bucci, Domenico; Busceti, Carla L.; Calierno, Maria T.; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

2017-01-01

Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology. PMID:29163071

Evaluation of quantitative parameters for distinguishing pheochromocytoma from other adrenal tumors.

PubMed

Ohno, Youichi; Sone, Masakatsu; Taura, Daisuke; Yamasaki, Toshinari; Kojima, Katsutoshi; Honda-Kohmo, Kyoko; Fukuda, Yorihide; Matsuo, Koji; Fujii, Toshihito; Yasoda, Akihiro; Ogawa, Osamu; Inagaki, Nobuya

2018-03-01

Adrenal tumors are increasingly found incidentally during imaging examinations. It is important to distinguish pheochromocytomas from other adrenal tumors because of the risk of hypertensive crisis. Although catecholamines and their metabolites are generally used to diagnose pheochromocytoma, false-positive test results are common. An effective screening method to distinguish pheochromocytoma from adrenal incidentalomas is needed. We analyzed 297 consecutive patients with adrenal incidentalomas. Our findings included 162 non-functioning tumors, 47 aldosterone-producing adenomas, 26 metastases, 22 cases of subclinical Cushing's syndrome, 21 pheochromocytomas, 12 cases of Cushing's syndrome, and 7 adrenocortical cancers. We checked quantitative parameters such as age, blood, and urine catecholamines and their metabolites, neuron-specific enolase, size and computed tomography (CT) attenuation values. Among catecholamine-related parameters, the sum of urine metanephrine and normetanephrine (urineMNM) levels produced the highest area under the receiver operating characteristic curve regarding discrimination of pheochromocytoma from other lesions. Size and CT attenuation values also differed significantly. However, size was correlated with catecholamine levels. CT attenuation was not correlated with other factors. The optimal thresholds were 19 Hounsfield units (HU) for CT attenuation (sensitivity, 100%; specificity, 60%) and 0.43 mg/24 h for urineMNM (sensitivity, 89%; specificity, 96%). No pheochromocytomas were evident when CT attenuation values were under 19 HU. Even in adrenal tumors with CT attenuation values ≥ 19 HU, when urineMNM was < 0.43 mg/24 h, the frequency of pheochromocytoma was only 4.3%, when urineMNM was ≥ 0.43 mg/24 h, the frequency of pheochromocytoma was 93% and when urineMNM was > 0.77 mg/24 h the frequency of pheochromocytoma was 100%. CT attenuation value and urineMNM represented the most useful combination for diagnosis of pheochromocytoma.

Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons

PubMed Central

Gioio, Anthony E.

2017-01-01

Abstract Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3′untranslated region (3’UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis-acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal. PMID:28630892

Brain catecholamine depletion and motor impairment in a Th knock-in mouse with type B tyrosine hydroxylase deficiency.

PubMed

Korner, Germaine; Noain, Daniela; Ying, Ming; Hole, Magnus; Flydal, Marte I; Scherer, Tanja; Allegri, Gabriella; Rassi, Anahita; Fingerhut, Ralph; Becu-Villalobos, Damasia; Pillai, Samyuktha; Wueest, Stephan; Konrad, Daniel; Lauber-Biason, Anna; Baumann, Christian R; Bindoff, Laurence A; Martinez, Aurora; Thöny, Beat

2015-10-01

Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons.

PubMed

Gervasi, Noreen M; Scott, Shane S; Aschrafi, Armaz; Gale, Jenna; Vohra, Sanah N; MacGibeny, Margaret A; Kar, Amar N; Gioio, Anthony E; Kaplan, Barry B

2016-06-01

Synthesis and regulation of catecholamine neurotransmitters in the central nervous system are implicated in the pathogenesis of a number of neuropsychiatric disorders. To identify factors that regulate the presynaptic synthesis of catecholamines, we tested the hypothesis that the rate-limiting enzyme of the catecholamine biosynthetic pathway, tyrosine hydroxylase (TH), is locally synthesized in axons and presynaptic nerve terminals of noradrenergic neurons. To isolate pure axonal mRNA and protein, rat superior cervical ganglion sympathetic neurons were cultured in compartmentalized Campenot chambers. qRT-PCR and RNA in situ hybridization analyses showed that TH mRNA is present in distal axons. Colocalization experiments with nerve terminal marker proteins suggested that both TH mRNA and protein localize in regions of the axon that resemble nerve terminals (i.e., synaptic boutons). Analysis of polysome-bound RNA showed that TH mRNA is present in polysomes isolated from distal axons. Metabolic labeling of axonally synthesized proteins labeled with the methionine analog, L-azidohomoalanine, showed that TH is locally synthesized in axons. Moreover, the local transfection and translation of exogenous TH mRNA into distal axons facilitated axonal dopamine synthesis. Finally, using chimeric td-Tomato-tagged constructs, we identified a sequence element within the TH 3'UTR that is required for the axonal localization of the reporter mRNA. Taken together, our results provide the first direct evidence that TH mRNA is trafficked to the axon and that the mRNA is locally translated. These findings raise the interesting possibility that the biosynthesis of the catecholamine neurotransmitters is locally regulated in the axon and/or presynaptic nerve terminal. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Disruption of the Axonal Trafficking of Tyrosine Hydroxylase mRNA Impairs Catecholamine Biosynthesis in the Axons of Sympathetic Neurons.

PubMed

Aschrafi, Armaz; Gioio, Anthony E; Dong, Lijin; Kaplan, Barry B

2017-01-01

Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal. Toward this end, a targeted deletion of the axonal transport sequence element was developed, using the lentiviral delivery of the CRISPR/Cas9 system, and two guide RNA (gRNA) sequences flanking the 50-bp cis- acting regulatory element in rat superior cervical ganglion (SCG) neurons. Deletion of the axonal transport element reduced TH mRNA levels in the distal axons and reduced the axonal protein levels of TH and TH activity as measured by phosphorylation of SER40 in SCG neurons. Moreover, deletion of the zip-code diminished the axonal levels of dopamine (DA) and norepinephrine (NE). Conversely, the local translation of exogenous TH mRNA in the distal axon enhanced TH levels and activity, and elevated axonal NE levels. Taken together, these results provide direct evidence to support the hypothesis that TH mRNA trafficking and local synthesis of TH play an important role in the synthesis of catecholamines in the axon and presynaptic terminal.

Cross-functioning between the extraneuronal monoamine transporter and multidrug resistance protein 1 in the uptake of adrenaline and export of 5-(glutathion-S-yl)adrenaline in rat cardiomyocytes.

PubMed

Costa, Vera Marisa; Ferreira, Lusa Maria; Branco, Paula Srio; Carvalho, Flix; Bastos, Maria Lourdes; Carvalho, Rui Albuquerque; Carvalho, Mrcia; Remio, Fernando

2009-01-01

Isolated heart cells are highly susceptible to the toxicity of catecholamine oxidation products, namely, to catecholamine-glutathione adducts. Although cellular uptake and/or efflux of these products may constitute a crucial step, the knowledge about the involvement of transporters is still very scarce. This work aimed to contribute to the characterization of membrane transport mechanisms, namely, extraneuronal monoamine transporter (EMT), the multidrug resistant protein 1 (MRP1), and P-glycoprotein (P-gp) in freshly isolated cardiomyocytes from adult rats. These transporters may be accountable for uptake and/or efflux of adrenaline and an adrenaline oxidation product, 5-(glutathion-S-yl)adrenaline, in cardiomyocyte suspensions. Our results showed that 5-(glutathion-S-yl)adrenaline efflux was mediated by MRP1. Additionally, we demonstrated that the adduct formation occurs within the cardiomyocytes, since EMT inhibition reduced the intracellular adduct levels. The classical uptake2 transport in rat myocardial cells was inhibited by the typical EMT inhibitor, corticosterone, and surprisingly was also inhibited by low concentrations of another drug, a well-known P-gp inhibitor, GF120918. The P-gp activity was absent in the cells since P-gp-mediated efflux of quinidine was not blocked by GF120918. In conclusion, this work showed that freshly isolated cardiomyocytes from adult rats constitute a good model for the study of catecholamines and catecholamines metabolites membrane transport. The cardiomyocytes maintain EMT and MRP1 fully active, and these transporters contribute to the formation and efflux of 5-(glutathion-S-yl)adrenaline. In the present experimental conditions, P-gp activity is absent in the isolated cardiomyocytes.

Ordering pattern and performance of biochemical tests for diagnosing pheochromocytoma between 2000 and 2008.

PubMed

Yu, Run

2009-01-01

To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation.

Behavioral and perceived stressor effects on urinary catecholamine excretion in adult Samoans.

PubMed

Bergey, Meredith R; Steele, Matthew S; Bereiter, David A; Viali, Satupaitea; McGarvey, Stephen T

2011-01-01

The effects of perceptions and behaviors related to culturally patterned socioeconomic obligations on catecholamine excretion rates were studied in a cross-sectional sample of Samoan adults. A total of 378 participants, ages 29-62 years, from 9 villages throughout Samoa, provided timed overnight urine specimens, and self-reported perceptions and behaviors associated with contributions to one's family, aiga, and chief, matai, and communal gift exchanges, fa'alavelave. Urinary norepinephrine and epinephrine excretion rates were measured by high performance liquid chromatography with electrochemical detection. Age (≤40 vs. >40 years) and gender-specific regression models were estimated to detect associations with catecholamine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who view their contribution to their matai to be "just right," had significantly higher residence-adjusted norepinephrine excretion. Young women who contribute more to their matai, who consider fa'alavelave to be a financial strain, and who consider their contribution to their aiga not to be a burden, had higher epinephrine excretion. Older men who contribute more to their aiga and who perceive their contribution to their aiga to be "just right" had increased residence-adjusted epinephrine excretion. Individual-level perceptions and behaviors related to traditional socioeconomic obligations are a significant correlate of increased overnight catecholamine excretion rates. Higher excretion rates may be attributed to psychosocial stress arousal associated with a discordance between personal desires for upward social mobility, and family and community-based socioeconomic obligations. Changes in patterns of individual-level psychosocial stress arousal may contribute to cardiovascular disease risk in modernizing Samoans. Copyright © 2011 Wiley-Liss, Inc.

Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity.

PubMed

Ríha, Michal; Vopršalová, Marie; Pilařová, Veronika; Semecký, Vladimír; Holečková, Magdalena; Vávrová, Jaroslava; Palicka, Vladimir; Filipský, Tomáš; Hrdina, Radomír; Nováková, Lucie; Mladěnka, Přemysl

2014-09-01

Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar-Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1). Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive cardiovascular effects.

Overnight Changes of Immune Parameters and Catecholamines Are Associated With Mood and Stress

PubMed Central

Rief, Winfried; Mills, Paul J.; Ancoli-Israel, Sonia; Ziegler, Michael G.; Pung, Meredith A.; Dimsdale, Joel E.

2011-01-01

Objectives To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables. Methods A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day. Results The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue rp = −.25 to −.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable. Conclusions The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted. PMID:20841563

Overnight changes of immune parameters and catecholamines are associated with mood and stress.

PubMed

Rief, Winfried; Mills, Paul J; Ancoli-Israel, Sonia; Ziegler, Michael G; Pung, Meredith A; Dimsdale, Joel E

2010-10-01

To test the hypothesis that a nocturnal decrease of secretion of inflammation markers and catecholamines would be associated with mood and stress variables even after controlling for objective sleep variables. A total of 130 healthy volunteers participated in this study, spending 2 nights in the Gillin Laboratory of Sleep and Chronobiology at the University of California, San Diego, General Clinical Research Center. Blood samples were obtained before sleep (10:30 PM) and after awakening (6:30 AM) on the first day, and these samples were assayed for inflammatory biomarkers and catecholamines. On the second night, polysomnographic records were scored for objective sleep variables, e.g., total sleep time and wake after sleep onset. Self-rating scales for mood, stress, depression, and daily hassles were administered the second day. The nocturnal decrease in interleukin-6 was smaller in people who reported more negative mood or fatigue and greater in those who reported more uplift events (e.g., with Profile of Mood States fatigue r(p) = -.25 to -.30). People with high stress or high depression levels had smaller nocturnal decreases of epinephrine. That relationship was even stronger when partial correlations were used to control for morning level and sleep variables. The associations between nocturnal changes of C-reactive protein, soluble tumor necrosis factor-receptor I, and norepinephrine with psychological states were nonremarkable. The analyses of nocturnal change scores (difference scores) add substantial information compared with the traditional analyses of morning levels of immune variables and catecholamines alone. Subjective well-being is significantly associated with a greater nocturnal decrease of interleukin-6 and epinephrine. More research on nocturnal adaptation processes is warranted.

On the mechanism of tachyphylaxis to tyramine in the isolated rat heart

PubMed Central

Axelrod, J.; Gordon, Edna; Hertting, G.; Kopin, I. J.; Potter, L. T.

1962-01-01

Tyramine was shown to release [3H]-catecholamines from an isolated rat heart previously perfused with [3H]-noradrenaline. With successive injections of tyramine the amount of [3H]-catecholamine released fell progressively and there was a parallel decrease in the increment of amplitude and rate of contraction of the heart. Reserpinized hearts were shown to take up less [3H]-noradrenaline than normal hearts. Release of radioactivity and loss of responsiveness to tyramine occurred more rapidly in the reserpinized heart. In the same preparation the uptake of [14C]-tyramine exceeded the quantity of the noradrenaline released. ImagesFig. 4 PMID:13863453

Catecholamine-mediated arrhythmias in acute myocardial infarction. Experimental evidence and role of beta-adrenoceptor blockade.

PubMed

Opie, L H; Lubbe, W F

1979-11-24

Ventricular fibrillation is a major mechanism of sudden death. The cellular link between catecholamine activity and the development of serious ventricular arrhythmias may be in the formation of cyclic adenosine monophosphate (cAMP). Cyclic AMP and agents promoting cAMP accumulation allow development of slow responses which, especially in the presence of regional ischaemia, could develop into ventricular fibrillation. The role of beta-antagonist agents in the therapy of acute myocardial infarction is analysed in relation to the hypothesis linking cAMP and ventricular fibrillation. Reasons for the limited effectiveness of anti-arrhythmic therapy with beta-antagonist agents are given.

Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

PubMed

Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

2016-01-01

The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons.

PubMed

Spencer, Jeremy P E; Whiteman, Matthew; Jenner, Peter; Halliwell, Barry

2002-04-01

A decrease in reduced glutathione levels in dopamine containing nigral cells in Parkinson's disease may result from the formation of cysteinyl-adducts of catecholamines, which in turn exert toxicity on nigral cells. We show that exposure of neurons (CSM 14.1) to 5-S-cysteinyl conjugates of dopamine, L-DOPA, DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base modification and an elevation of caspase-3 activity in cells. Damage to neurons was apparent 12-48 h of post-exposure and there were increases in caspase-3 activity in neurons after 6 h. These changes were paralleled by large increases in pyrimidine and purine base oxidation products, such as 8-OH-guanine suggesting that 5-S-cysteinyl conjugates of catecholamines are capable of diffusing into cells and stimulating the formation of reactive oxygen species (ROS), which may then lead to a mechanism of cell damage involving caspase-3. Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease.

Effects of active recovery during interval training on plasma catecholamines and insulin.

PubMed

Nalbandian, Harutiun M; Radak, Zsolt; Takeda, Masaki

2018-06-01

BACKGROUNDː Active recovery has been used as a method to accelerate the recovery during intense exercise. It also has been shown to improve performance in subsequent exercises, but little is known about its acute effects on the hormonal and metabolic profile. The aim of this research was to study the effects of active recovery on plasma catecholamines and plasma insulin during a high-intensity interval exercise. METHODSː Seven subjects performed two high-intensity interval training protocols which consisted of three 30-second high-intensity bouts (constant intensity), separated by a recovery of 4 minutes. The recovery was either active recovery or passive recovery. During the main test blood samples were collected and plasma insulin, plasma catecholamines and blood lactate were determined. Furthermore, respiratory gasses were also measured. RESULTSː Plasma insulin and blood lactate were significantly higher in the passive recovery trial, while plasma adrenaline was higher in the active recovery. Additionally, VO2 and VCO2 were significantly more increased during the active recovery trials. CONCLUSIONSː These results suggest that active recovery affects the hormonal and metabolic responses to high-intensity interval exercise. Active recovery produces a hormonal environment which may favor lipolysis and oxidative metabolism, while passive recovery may be favoring glycolysis.

Alpha-1-Adrenergic Receptors in Heart Failure: The Adaptive Arm of the Cardiac Response to Chronic Catecholamine Stimulation

PubMed Central

Jensen, Brian C.; O'Connell, Timothy D.; Simpson, Paul C.

2013-01-01

Alpha-1-adrenergic receptors are G-protein coupled receptors (GPCRs) activated by catecholamines. The alpha-1A and alpha-1B subtypes are expressed in mouse and human myocardium, whereas the alpha-1D protein is found only in coronary arteries. There are far fewer alpha-1-ARs than beta-ARs in the non-failing heart, but their abundance is maintained or increased in the setting of heart failure, which is characterized by pronounced chronic elevation of catecholamines and b□eta-AR dysfunction. Decades of evidence from gain- and loss-of-function studies in isolated cardiac myocytes and numerous animal models demonstrate important adaptive functions for cardiac alpha-1-ARs, to include physiological hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Clinical trial data indicate that blocking alpha-1-ARs is associated with incident heart failure in patients with hypertension. Collectively, these findings suggest that alpha-1-AR activation might mitigate the well-recognized toxic effects of beta-ARs in the hyperadrenergic setting of chronic heart failure. Thus, exogenous cardioselective activation of alpha-1-ARs might represent a novel and viable approach to the treatment of heart failure. PMID:24145181

Chromogranin A deficiency in transgenic mice leads to aberrant chromaffin granule biogenesis.

PubMed

Kim, Taeyoon; Zhang, Chun-fa; Sun, Ziqing; Wu, Heling; Loh, Y Peng

2005-07-27

The biogenesis of dense-core secretory granules (DCGs), organelles responsible for the storage and secretion of neurotransmitters and neuropeptides in chromaffin cells, is poorly understood. Chromogranin A (CgA), which binds catecholamines for storage in the lumen of chromaffin granules, has been shown to be involved in DCG biogenesis in neuroendocrine PC12 cells. Here, we report that downregulation of CgA expression in vivo by expressing antisense RNA against CgA in transgenic mice led to a significant reduction in DCG formation in adrenal chromaffin cells. The number of DCGs formed in CgA antisense transgenic mice was directly correlated with the amount of CgA present in adrenal medulla. In addition, DCGs showed an increase in size, with enlargement in the volume around the dense core, a phenomenon that occurs to maintain constant "free" catecholamine concentration in the lumen of these granules. The extent of DCG swelling was inversely correlated with the number of DCGs formed, as well as the amount of CgA present in the adrenal glands of CgA antisense transgenic mice. These data indicate an essential role of CgA in regulating chromaffin DCG biogenesis and catecholamine storage in vivo.

Synergy between growth factors and transmitters required for catecholamine differentiation in brain neurons.

PubMed

Du, X; Iacovitti, L

1995-07-01

The phenotypically plastic neurons of the embryonic mouse striatum were used to explore mechanisms of catecholamine differentiation in culture. De novo transcription and translation of the CA biosynthetic enzyme, tyrosine hydroxylase (TH), was induced in striatal neurons exposed, simultaneously or sequentially, to the growth factor, acidic fibroblast growth factor (aFGF) and a catecholamine. Although dopamine was the most potent aFGF partner (ED50 = 4 microM), a number of substances, including dopamine (D1) receptor agonists, beta-adrenoceptor agonists, and dopamine uptake inhibitors also trigger TH induction when accompanied by aFGF. However, since none of the receptor antagonists nor transport blockers tested could inhibit dopamine's action, the mechanism remains obscure. Structure-activity analysis suggests that effective aFGF partners all contain an amine group separated from a catechol nucleus by two carbons. Thus, TH expression can be novelly induced by the synergistic interaction of aFGF, and to a lesser extent basic FGF, and a variety of CA-containing partner molecules. We speculate that a similar association between growth factor and transmitter may be required in development for the differentiation of a CA phenotype in brain neurons.

Inhibition of Ca2+ channels and adrenal catecholamine release by G protein coupled receptors.

PubMed

Currie, Kevin P M

2010-11-01

Catecholamines and other transmitters released from adrenal chromaffin cells play central roles in the "fight-or-flight" response and exert profound effects on cardiovascular, endocrine, immune, and nervous system function. As such, precise regulation of chromaffin cell exocytosis is key to maintaining normal physiological function and appropriate responsiveness to acute stress. Chromaffin cells express a number of different G protein coupled receptors (GPCRs) that sense the local environment and orchestrate this precise control of transmitter release. The primary trigger for catecholamine release is Ca2+ entry through voltage-gated Ca2+ channels, so it makes sense that these channels are subject to complex regulation by GPCRs. In particular G protein βγ heterodimers (Gbc) bind to and inhibit Ca2+ channels. Here I review the mechanisms by which GPCRs inhibit Ca2+ channels in chromaffin cells and how this might be altered by cellular context. This is related to the potent autocrine inhibition of Ca2+ entry and transmitter release seen in chromaffin cells. Recent data that implicate an additional inhibitory target of Gβγ on the exocytotic machinery and how this might fine tune neuroendocrine secretion are also discussed.

Transmitter responsiveness in two newly isolated clones of neuroblastoma X glioma hybrid.

PubMed

Ogura, A; Amano, T

1983-01-10

Mouse neuroblastoma clone N1E-115 cells and rat glioma clone C6 cells were hybridized and two new clones were isolated. One clone, designated NG115-301, possessed weak electric excitability to an applied current pulse, while another clone, NG115-401, generated an action potential in response to the pulse. The former clone responded to serotonin and catecholamines with slow hyperpolarizations, while the latter clone responded to catecholamines with transient depolarizations. Both clones did not respond to acetylcholine. These types of responses have not been reported in any available clones. These clones may enrich the repertoire of cell clones useful for the characterization of transmitter reception mechanisms in the nervous system.

Hormonal responses of pilots flying high-performance aircraft during seven repetitive flight missions.

PubMed

Tarui, H; Nakamura, A

1991-12-01

Hormonal responses during seven repetitive flight missions (7RFM) were evaluated on F-4EJ fighter pilots. The following biochemical constituents were measured: 1) cortisol in saliva; 2) 17-OHCS; 3) unbound cortisol; 4) catecholamines in urine; and 5) electrolytes in urine. Samples were collected at about 30 min before the mission, 20 min after each flight, and in a nonflight day for control. The levels of saliva and urine corticosteroids slightly increased during 7RFM when compared with controls. The concentrations of urine catecholamines during 7RFM were significantly higher than those of preflight and control. These data suggest that flight stresses were moderate for the pilots flying 7RFM.

The role of prefrontal catecholamines in attention and working memory

PubMed Central

Clark, Kelsey L.; Noudoost, Behrad

2014-01-01

While much progress has been made in identifying the brain regions and neurochemical systems involved in the cognitive processes disrupted in mental illnesses, to date, the level of detail at which neurobiologists can describe the chain of events giving rise to cognitive functions is very rudimentary. Much of the intense interest in understanding cognitive functions is motivated by the hope that it might be possible to understand these complex functions at the level of neurons and neural circuits. Here, we review the current state of the literature regarding how modulations in catecholamine levels within the prefrontal cortex (PFC) alter the neuronal and behavioral correlates of cognitive functions, particularly attention and working memory. PMID:24782714

Unusual case of pheochromocytoma presenting with diabetic ketoacidosis.

PubMed

Sedhai, Yub Raj; Reddy, Kruthika; Patel, Dhruvan; Lozada, James A

2016-10-19

Pheochromocytoma is a rare catecholamine-secreting tumour that arises from chromaffin cells in the adrenal medulla or extra-adrenal sympathetic ganglia. It classically presents with paroxysmal headaches, hypertension, palpitations and sweating related to catecholamine excess. Diabetes is reported to be present in approximately one-third of patients with pheochromocytoma; however, diabetic ketoacidosis is an extremely rare complication. We present a case of an African-American male aged 30 years who initially presented with diabetic ketoacidosis and hypertensive urgency whose blood pressure and glycaemic control improved remarkably following tumour excision. We will discuss this unusual presentation of pheochromocytoma along with a management approach for such adrenal incidentalomas. 2016 BMJ Publishing Group Ltd.

Receptor mechanisms in fish chromatophores--VII. Muscarinic cholinoceptors and alpha adrenoceptors, both mediating pigment aggregation, strangely coexist in Corydoras melanophores.

PubMed

Kasukawa, H; Fujii, R

1985-01-01

Both acetylcholine and catecholamines showed melanin-aggregating action within melanophores on an isolated bony plate of the mailed catfish Corydoras paleatus. Chromatic nervous stimulation either by an electrical field or by an elevation of [K+]0 brought about melanosome aggregation. Alpha adrenolytic agents antagonized the melanin-aggregating effects either of catecholamines or of nervous stimuli. Muscarinic cholinolytics interfered with the action of acetylcholine, but did not have any effect on the responses to nervous stimuli. In addition to the alpha adrenoceptors which participate in sympathetic-melanophore transmission, muscarinic cholinoceptors of unknown functional significance, which also mediate melanosome aggregation in the cell, exist in Corydoras melanophores.

Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

NASA Technical Reports Server (NTRS)

Wurtman, Richard J.

1988-01-01

Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys.

PubMed

Oemisch, Mariann; Johnston, Kevin; Paré, Martin

2016-10-01

Working memory is a limited-capacity cognitive process that retains relevant information temporarily to guide thoughts and behavior. A large body of work has suggested that catecholamines exert a major modulatory influence on cognition, but there is only equivocal evidence of a direct influence on working memory ability, which would be reflected in a dependence on working memory load. Here we tested the contribution of catecholamines to working memory by administering a wide range of acute oral doses of the dopamine and norepinephrine reuptake inhibitor methylphenidate (MPH, 0.1-9 mg/kg) to three female macaque monkeys (Macaca mulatta), whose working memory ability was measured from their performance in a visual sequential comparison task. This task allows the systematic manipulation of working memory load, and we therefore tested the specific hypothesis that MPH modulates performance in a manner that depends on both dose and memory load. We found no evidence of a dose- or memory load-dependent effect of MPH on performance. In contrast, significant effects on measures of motivation were observed. These findings suggest that an acute increase in catecholamines does not seem to affect the retention of visual information per se. As such, these results help delimit the effects of MPH on cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors.

PubMed

Combet, Emilie; Lean, Michael E J; Boyle, James G; Crozier, Alan; Davidson, D Fraser

2011-01-14

Urinary homovanillic acid (HVA) measurement is used routinely as a marker of the first test for the screening of catecholamine-secreting tumors and dopamine metabolism, but generates a large number of false-positive results. With no guidelines for dietary restrictions prior to the test, we hypothesize that consumption of flavonol-rich foods (such as onions, tomatoes, tea) prior to urinary catecholamine screening could be responsible for false-positive urinary HVA in healthy subjects. A randomized, crossover dietary intervention was carried out in healthy subjects (n=17). Volunteers followed either a low or high-flavonol diet, for a duration of 3 days, prior to providing a 24-h urine sample for HVA measurement using a routine, validated liquid chromatography method as well as a gas chromatography-mass spectrometry method. Dietary flavonol intake significantly increased urinary HVA excretion (p < 0.001), with 3 out of 17 volunteers (20%) exceeding the 40 μmol/24 h upper limit of normal for HVA excretion (false-positive result). Dietary flavonols commonly found in foodstuff such as tomatoes, onions, and tea, interfered with the routine urinary HVA screening test and should be avoided in the three-day run-up to the test. Copyright © 2010 Elsevier B.V. All rights reserved.

Acute stress cardiomyopathy and deaths associated with electronic weapons.

PubMed

Cevik, Cihan; Otahbachi, Mohammad; Miller, Elizabeth; Bagdure, Satish; Nugent, Kenneth M

2009-03-06

Deaths associated with the use of electronic weapons almost always occur in young men involved in either civil disturbances or criminal activity. These situations are associated with high levels of circulating catecholamines and frequently associated with drug intoxication. The mechanism for these deaths is unclear. Clinical studies indicate that these high voltage electrical pulses do not cause cardiac arrhythmia. Acute stress cardiomyopathy provides an alternative explanation for deaths associated with electronic weapons and may provide a better explanation for the usual time course associated with taser deaths. Patients with acute stress cardiomyopathy usually have had an emotional or physical stress, have high circulating levels of catecholamines, present with an acute coronary syndrome but have normal coronary vessels without significant thrombus formation. They have unusual left ventricular dysfunction with so-called apical ballooning. This presentation has been attributed to the direct effects of catecholamines on myocardial cell function. Alternative explanations include vasospasm in the coronary microcirculation and/or acute thrombosis followed by rapid thrombolysis. Similar events could occur during the high stress situations associated with the use of electronic weapons. These events also likely explain restraint-related deaths which occur in independent of any use of electronic weapons. Forensic pathologists have the opportunity to provide important details about the pathogenesis of these deaths through histological studies and careful evaluation of coronary vessels.

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients.

PubMed

Slob, Elise M A; Shulman, Rob; Singer, Mervyn

2017-10-01

To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia (>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation. Copyright © 2017. Published by Elsevier Inc.

Energy balance studies and plasma catecholamine values for patients with healed burns.

PubMed

Wallace, B H; Cone, J B; Caldwell, F T

1991-01-01

We report heat balance studies and plasma catecholamine values for 49 children and young adults with healed burn wounds (age range 0.6 to 31 years and burn range 1% to 82% body surface area burned; mean 41%). All measurements were made during the week of discharge. Heat production for patients with healed burns was not significantly different from predicted normal values. However, compartmented heat loss demonstrated a persistent increment in evaporative heat loss that was secondary to continued elevation of cutaneous water vapor loss immediately after wound closure. A reciprocal decrement in dry heat loss was demonstrated (as a result of a cooler average surface temperature, 0.84 degree C cooler than the average integrated skin temperature of five normal volunteers who were studied in our unit under similar environmental conditions). Mean values for plasma catecholamines were in the normal range: epinephrine = 56 +/- 37 pg/ml, norepinephrine = 385 +/- 220 pg/ml, and dopamine = 34 +/- 29 pg/ml. In conclusion, patients with freshly healed burn wounds have normal rates of heat production; however, there is a residual increment in transcutaneous water vapor loss, which produces surface cooling and decreased average surface temperature, which in turn lowers dry heat loss by an approximately equivalent amount.

Response to pentagastrin after acute phenylalanine and tyrosine depletion in healthy men: a pilot study.

PubMed Central

Coupland, N; Zedkova, L; Sanghera, G; Leyton, M; Le Mellédo, J M

2001-01-01

OBJECTIVE: To assess the effects of the acute depletion of the catecholamine precursors phenylalanine and tyrosine on mood and pentagastrin-induced anxiety. DESIGN: Randomized, double-blind controlled multiple crossover study. SETTING: University department of psychiatry. PARTICIPANTS: 6 healthy male volunteers. INTERVENTIONS: 3 treatments were compared: pretreatment with a nutritionally balanced amino acid mixture, followed 5 hours later by a bolus injection of normal saline placebo; pretreatment with a balanced amino acid mixture, followed by a bolus injection of pentagastrin (0.6 microgram/kg); and pretreatment with an amino acid mixture without the catecholamine precursors phenylalanine or tyrosine, followed by pentagastrin (0.6 microgram/kg). OUTCOME MEASURES: Scores on the panic symptom scale, a visual analogue scale for anxiety, the Borg scale of respiratory exertion and the Profile of Mood States Elation-Depression Scale. RESULTS: Pentagastrin produced the expected increases in anxiety symptoms, but there was no significant or discernible influence of acute phenylalanine and tyrosine depletion on anxiety or mood. CONCLUSIONS: These pilot data do not support further study using the same design in healthy men. Under these study conditions, phenylalanine and tyrosine depletion may have larger effects on dopamine than noradrenaline. Alternative protocols to assess the role of catecholamines in mood and anxiety are proposed. PMID:11394194

Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia.

PubMed

Ishikawa, Takaki; Yoshida, Chiemi; Michiue, Tomomi; Perdekamp, Markus Grosse; Pollak, Stefan; Maeda, Hitoshi

2010-05-01

Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of adrenergic stimulation on ventilation in man

PubMed Central

Heistad, Donald D.; Wheeler, Robert C.; Mark, Allyn L.; Schmid, Phillip G.; Abboud, Francois M.

1972-01-01

The mechanism by which catecholamines affect ventilation in man is not known. Ventilatory responses to catecholamines were observed in normal subjects before and after adrenergic receptor blockade. Intravenous infusions of norepinephrine and isoproterenol caused significant increases in minute volume and decreases in end-tidal PCo2 which were blocked by the administration of propranolol, a beta adrenergic receptor blocker. The hyperventilatory response to hypoxia was not altered by propranolol. Intravenous infusion of phenylephrine caused a small but significant decrease in minute volume which was antagonized by phentolamine, an alpha adrenergic receptor blocker. Angiotensin, a nonadrenergic pressor agent, also decreased minute volume significantly. 100% oxygen was administered to suppress arterial chemoreceptors. Increases in minute volume and decreases in arterial PCo2 in response to norepinephrine and isoproterenol were blocked by breathing 100% oxygen. The decrease in minute volume during phenylephrine was not altered by 100% oxygen. The results indicate that: (a) beta adrenergic receptors mediate the hyperventilatory response to norepinephrine and isoproterenol but not to hypoxia. (b) the pressor agents phenylephrine and angiotensin decrease ventilation, and (c) suppression of chemoreceptors blocks the ventilatory response to norepinephrine and isoproterenol but not to phenylephrine. Implications concerning the interaction of adrenergic receptors and chemoreceptors with respect to the hyperventilatory response to catecholamines are discussed. PMID:4336940

N-(4-Trifluoromethylphenyl)amide group of the synthetic histamine receptor agonist inhibits nicotinic acetylcholine receptor-mediated catecholamine secretion.

PubMed

Kim, Dong-Chan; Park, Yong-Soo; Jun, Dong-Jae; Hur, Eun-Mi; Kim, Sun-Hee; Choi, Bo-Hwa; Kim, Kyong-Tai

2006-02-28

The therapeutic targeting of nicotinic receptors requires the identification of drugs that selectively activate or inhibit a limited range of nicotine acetylcholine receptors (nAChRs). In this study, we identified N-(4-trifluoromethylphenyl)amide group of the synthetic histamine receptor ligands, histamine-trifluoromethyltoluide, that act as potent inhibitors of nAChRs in bovine adrenal chromaffin cells. Catecholamine secretion induced by the nAChRs agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), was significantly inhibited by histamine-trifluoromethyltoluide. Real time carbon-fiber amperometry confirmed the ability of histamine-trifluoromethyltoluide to inhibit DMPP-induced exocytosis in single chromaffin cells. We also found that histamine-trifluoromethyltoluide inhibited DMPP-induced [Ca(2+)](i) and [Na(+)](i) increases, as well as DMPP-induced inward currents in the absence of extracellular calcium. Histamine-trifluoromethyltoluide had no effect on [(3)H]nicotine binding or on calcium increases induced by high K(+), bradykinin, veratridine, histamine, and benzoylbenzoyl ATP. Among the synthetic histamine receptor ligands, clobenpropit exhibited similarity. In addition, 4'-nitroacetanilide also significantly attenuated nAChR-mediated catecholamine secretion. In conclusion, the N-(4-trifluoromethylphenyl)amide group of the histamine-trifluoromethyltoluide might be the critical moiety in the inhibition of nAChR-mediated CA secretion.

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

PubMed

Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

2001-12-01

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

Psychological stress-induced changes in salivary alpha-amylase and adrenergic activity.

PubMed

Kang, Younhee

2010-12-01

The aim of the study was to examine the relationships among salivary alpha-amylase, plasma catecholamines, blood pressure, and heart rate during psychological stress. This study used a pretest-post-test experimental design with a control group, using repeated measures. A total of 33 participants was divided into the experimental group (n = 16) that underwent a college academic final test as the psychological stress and the control group (n = 17) that did not undergo the test. The levels of salivary alpha-amylase and plasma catecholamines, blood pressure, and heart rate were measured seven times and stress and anxiety were measured once and twice, respectively, as subjective stress markers. Significant changes in the level of salivary alpha-amylase were found in response to psychological stress. However, the correlations of salivary alpha-amylase with the plasma catecholamines, blood pressure, and heart rate were only partially found to be statistically significant. In conclusion, it was shown that salivary alpha-amylase was sensitive to stress throughout this study. Thus, salivary alpha-amylase may be used to measure stress uninvasively in both clinical settings and nursing research where the effects of stress might be scrutinized. Furthermore, the mechanisms of illnesses that are induced by stress could be explored. © 2010 Blackwell Publishing Asia Pty Ltd.

Changes in sleep quality of athletes under normobaric hypoxia equivalent to 2,000-m altitude: a polysomnographic study.

PubMed

Hoshikawa, Masako; Uchida, Sunao; Sugo, Takayuki; Kumai, Yasuko; Hanai, Yoshiteru; Kawahara, Takashi

2007-12-01

This study evaluated the sleep quality of athletes in normobaric hypoxia at a simulated altitude of 2,000 m. Eight male athletes slept in normoxic condition (NC) and hypoxic conditions equivalent to those at 2,000-m altitude (HC). Polysomnographic recordings of sleep included the electroencephalogram (EEG), electrooculogram, chin surface electromyogram, and electrocardiogram. Thoracic and abdominal motion, nasal and oral airflow, and arterial blood oxygen saturation (Sa(O(2))) were also recorded. Standard visual sleep stage scoring and fast Fourier transformation analyses of the EEG were performed on 30-s epochs. Subjective sleepiness and urinary catecholamines were also monitored. Mean Sa(O(2)) decreased and respiratory disturbances increased with HC. The increase in respiratory disturbances was significant, but the increase was small and subclinical. The duration of slow-wave sleep (stage 3 and 4) and total delta power (<3 Hz) of the all-night non-rapid eye movement sleep EEG decreased for HC compared with NC. Subjective sleepiness and amounts of urinary catecholamines did not differ between the conditions. These results indicate that acute exposure to normobaric hypoxia equivalent to that at 2,000-m altitude decreased slow-wave sleep in athletes, but it did not change subjective sleepiness or amounts of urinary catecholamines.

Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

PubMed

Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Nakamura, Jun

2017-08-01

Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Sympathovagal imbalance in hyperthyroidism.

PubMed

Burggraaf, J; Tulen, J H; Lalezari, S; Schoemaker, R C; De Meyer, P H; Meinders, A E; Cohen, A F; Pijl, H

2001-07-01

We assessed sympathovagal balance in thyrotoxicosis. Fourteen patients with Graves' hyperthyroidism were studied before and after 7 days of treatment with propranolol (40 mg 3 times a day) and in the euthyroid state. Data were compared with those obtained in a group of age-, sex-, and weight-matched controls. Autonomic inputs to the heart were assessed by power spectral analysis of heart rate variability. Systemic exposure to sympathetic neurohormones was estimated on the basis of 24-h urinary catecholamine excretion. The spectral power in the high-frequency domain was considerably reduced in hyperthyroid patients, indicating diminished vagal inputs to the heart. Increased heart rate and mid-frequency/high-frequency power ratio in the presence of reduced total spectral power and increased urinary catecholamine excretion strongly suggest enhanced sympathetic inputs in thyrotoxicosis. All abnormal features of autonomic balance were completely restored to normal in the euthyroid state. beta-Adrenoceptor antagonism reduced heart rate in hyperthyroid patients but did not significantly affect heart rate variability or catecholamine excretion. This is in keeping with the concept of a joint disruption of sympathetic and vagal inputs to the heart underlying changes in heart rate variability. Thus thyrotoxicosis is characterized by profound sympathovagal imbalance, brought about by increased sympathetic activity in the presence of diminished vagal tone.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task.

PubMed

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-03-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. © The Author(s) 2016.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task

PubMed Central

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-01-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. PMID:26755547

Differential effects of catecholamines on in vitro growth of pathogenic bacteria

NASA Technical Reports Server (NTRS)

Belay, Tesfaye; Sonnenfeld, Gerald

2002-01-01

Supplementation of minimal medium inoculated with bacterial cultures with norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked increases in growth compared to controls. Norepinephrine and dopamine had the greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth to a lesser extent. The growth of Escherichia coli in the presence of norepinephrine was greater than growth in the presence of the three other neurochemicals used in the study. Growth of Staphylococcus aureus was also enhanced in the presence of norepinephrine, but not to the same degree as was the growth of gram negative bacteria. Addition of culture supernatants from E. coli cultures that had been grown in the presence of norepinephrine was able to enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid culture from E. coli cultures that had been grown in the presence of norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture supernatant fluids from bacteria other than E. coli grown in the presence of norepinephrine were not able to enhance the growth of any bacteria tested. The results suggest that catecholamines can enhance growth of pathogenic bacteria, which may contribute to development of pathogenesis; however, there is no uniform effect of catecholamines on bacterial growth.

Regulation of transepithelial ion transport in the rat late distal colon by the sympathetic nervous system.

PubMed

Zhang, X; Li, Y; Zhang, X; Duan, Z; Zhu, J

2015-01-01

The colorectum (late distal colon) is innervated by the sympathetic nervous system, and many colorectal diseases are related to disorders of the sympathetic nervous system. The sympathetic regulation of colorectal ion transport is rarely reported. The present study aims to investigate the effect of norepinephrine (NE) in the normal and catecholamine-depleted condition to clarify the regulation of the sympathetic adrenergic system in ion transport in the rat colorectum. NE-induced ion transport in the rats colorectum was measured by short-circuit current (I(sc)) recording; the expression of beta-adrenoceptors and NE transporter (NET) were quantified by real-time PCR, and western blotting. When the endogenous catecholamine was depleted by reserpine, the baseline I(sc) in the colorectum was increased significantly comparing to controls. NE evoked downward deltaI(sc) in colorectum of treated rats was 1.8-fold of controls. The expression of beta(2)-adrenoceptor protein in the colorectal mucosa was greater than the control, though the mRNA level was reduced. However, NET expression was significantly lower in catecholamine-depleted rats compared to the controls. In conclusion, the sympathetic nervous system plays an important role in regulating basal ion transport in the colorectum. Disorders of sympathetic neurotransmitters result in abnormal ion transport, beta-adrenoceptor and NET are involved in the process.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

A Case of Hypertensive Crisis without a Surge in Adrenal Hormones after Radiofrequency Ablation as a Treatment for Primary Hepatocellular Carcinoma.

PubMed

Lee, Kyung Jin; Ryu, Soo Hyung

2017-10-25

Radiofrequency ablation (RFA) is a minimally invasive procedure that has been considered as a relatively safe treatment for patients with small hepatocellular carcinoma (HCC). However, RFA has been shown to be associated with complications including mechanical and thermal damage. A 74-year-old man with hepatitis C virus-associated HCC was admitted to our hospital. Abdominal computed tomography revealed two lobulated-HCC in segments 4 and 5. He had no medical history of hypertension and cardiac disease. During RFA, blood pressure was elevated to 200/140 mmHg. There was no evidence of pulmonary embolism, aortic dissection, or ischemic heart disease. Laboratory findings for catecholamine surge were all within normal limits. After continuous intravenous nitroglycerin and oral beta-blocker treatment, patient's blood pressure gradually decreased and back within the normal range. Hypertensive crisis after RFA treatment for HCC is rare. Most reported cases of hypertensive crisis during RFA were related to adrenal gland injury with a release of catecholamine. In our case, the site of HCC was not close to the adrenal gland, and there was no evidence of catecholamine surge. Herein, we report a very rare case of hypertensive crisis without a surge in adrenal hormones after RFA treatment for HCC.

18F-FDOPA PET/CT uptake parameters correlate with catecholamines secretion in human pheochromocytomas.

PubMed

Moog, Sophie; Moog, Sophie; Houy, Sébastien; Chevalier, Elodie; Ory, Stéphane; Weryha, Georges; Rame, Marion; Klein, Marc; Brunaud, Laurent; Gasman, Stéphane; Cuny, Thomas

2018-06-27

Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM) and chromogranin A (CGA). Thirty-five patients were screened for germline mutations in RET, SDHx and VHL genes. Once resected, primary cultures of 5 PHEO were used for real time measurement of catecholamines release by carbon fiber amperometry. The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r=0.64, p<0.0001), MN (r=0.49, p=0.002), combined MN and NM (r=0.75, p<0,0001) and eventually plasma free levels of NM (r=0.55 p=0.006). In mutated-patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL and 3 RET), a similar correlation was observed between the MB and the 24h-urinary combined MN and NM (r=0.86, p=0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p=0.01). While the 18F-FDOPA PET/CT metabolic burden of PHEO strongly correlates with the concentration of metanephrines, amperometric recordings suggest that the 18F-FDOPA uptake could be enhanced by the overactivity of the catecholamines exocytosis.
. ©2018S. Karger AG, Basel.

Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Haoping; Wang, Hong; Ma, Shangwei

2014-01-01

Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectionalmore » regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p < 0.01), while it reduced 300 μM acetylcholine (ACh) (p < 0.01), 100 μM veratridine (Ver) (p < 0.01) and 56 mM K{sup +} (p < 0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p < 0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56 mM K{sup +} induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion. • Bakuchiol may have anti-stress and the potential anti-depression-like effects.« less

Hydroxylation increases the neurotoxic potential of BDE-47 to affect exocytosis and calcium homeostasis in PC12 cells.

PubMed

Dingemans, Milou M L; de Groot, Aart; van Kleef, Regina G D M; Bergman, Ake; van den Berg, Martin; Vijverberg, Henk P M; Westerink, Remco H S

2008-05-01

Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants. Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells. We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively. Acute exposure of PC12 cells to 6-OH-BDE-47 (5 microM) induced vesicular catecholamine release. Catecholamine release coincided with a transient increase in [Ca2+]i, which was observed shortly after the onset of exposure to 6-OH-BDE-47 (120 microM). An additional late increase in [Ca2+]i was often observed at > or =1 microM 6-OH-BDE-47. The initial transient increase was absent in cells exposed to the parent compound BDE-47, whereas the late increase was observed only at 20 microM. Using the mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and thapsigargin to empty intracellular Ca2+ stores, we found that the initial increase originates from emptying of the endoplasmic reticulum and consequent influx of extracellular Ca2+, whereas the late increase originates primarily from mitochondria. The hydroxylated metabolite 6-OH-BDE-47 is more potent in disturbing Ca2+ homeostasis and neurotransmitter release than the parent compound BDE-47. The present findings indicate that bioactivation by oxidative metabolism adds considerably to the neurotoxic potential of PBDEs. Additionally, based on the observed mechanism of action, a cumulative neurotoxic effect of PBDEs and ortho-substituted polychlorinated biphenyls on [Ca2+]i cannot be ruled out.

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

[Catecholamines and their metabolites in children with Asperger and Kanner syndromes].

PubMed

Gorina, A S; Kolesnichenko, L S; Mikhnovich, V I

2011-01-01

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

PubMed

Zumárraga, Mercedes; Arrúe, Aurora; Basterreche, Nieves; Macías, Isabel; Catalán, Ana; Madrazo, Arantza; Bustamante, Sonia; Zamalloa, María I; Erkoreka, Leire; Gordo, Estibaliz; Arnaiz, Ainara; Olivas, Olga; Arroita, Ariane; Marín, Elena; González-Torres, Miguel A

2016-06-01

We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

Flow-injection analysis of catecholamine secretion from bovine adrenal medulla cells on microbeads.

PubMed

Herrera, M; Kao, L S; Curran, D J; Westhead, E W

1985-01-01

Bovine adrenal medullary cells have been cultured on microbeads which are placed in a low-volume flow system for measurements of stimulation-response parameters. Electronically controlled stream switching allows stimulation of cells with pulse lengths from 1 s to many minutes; pulses may be repeated indefinitely. Catecholamines secreted are detected by an electrochemical detector downstream from the cells. This flow-injection analysis technique provides a new level of sensitivity and precision for measurement of kinetic parameters of secretion. A manual injection valve allows stimulation by higher levels of stimulant in the presence of constant low levels of stimulant. Such experiments show interesting differences between the effects of K+ and acetylcholine on cells partially desensitized to acetylcholine.

Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction.

PubMed

Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

2016-03-01

The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

Increased GAD67 mRNA levels are correlated with in vivo GABA synthesis in the MPTP-treated catecholamine-depleted goldfish brain.

PubMed

Hibbert, Benjamin; Fung, Irene; McAuley, Rebecca; Larivière, Katherine; MacNeil, Brian; Bafi-Yeboa, Nana; Livesey, John; Trudeau, Vance

2004-09-28

The role of catecholamine neuronal input on GABAergic activity in the hypothalamus, telencephalon, optic tectum, and cerebellum was investigated in early recrudescent female goldfish (Carassius auratus). A new quantitative technique was developed and validated, permitting concomitant quantification and correlational analysis of glutamic acid decarboxylase 65 (GAD65), GAD67, and GAD3 mRNA levels and in vivo GABA synthesis. Catecholamine depletion was achieved by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 microg/g body weight) and dopamine (DA) depletion verified by HPLC. Endogenous GABA levels were increased by intraperitoneal administration of gamma-vinyl GABA (GVG; 300 microg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Treatment with MPTP resulted in a greater than twofold increase in GABA synthesis rate in the optic tectum and telencephalon. The increase in GABA synthesis rate was highly correlated with an increase in GAD67, but not GAD65 or GAD3 mRNA levels. These results suggest that catecholaminergic input exerts inhibitory effects on GABA synthesis rates through the modulation of GAD67 in the optic tectum and telencephalon. Together with previously published observations in rodents and primates, it is suggested that catecholaminergic control of GABA synthesis must have evolved more than 200 million years ago, before the emergence of the teleost fishes.

A case of sleep apnea syndrome manifesting severe hypertension with high plasma norepinephrine levels.

PubMed

Makino, Shinya; Iwata, Masanobu; Fujiwara, Masayoshi; Ike, Shinpei; Tateyama, Hitone

2006-06-01

A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alpha-adrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma.

L-threo 3,4-dihydroxyphenylserine treatment during mouse perinatal and rat postnatal development does not alter the impact of dietary copper deficiency

PubMed Central

Pyatskowit, Joshua W.; Prohaska, Joseph R.

2009-01-01

Dietary copper (Cu) deficiency was induced perinatally in Swiss Albino mice and postnatally in male Holtzman rats to investigate the effect of L-threo 3,4-dihydroxyphenylserine (DOPS) on pup survival and catecholamine levels in a 2 × 2 factorial design. Mouse dams were placed on one of four treatments 14 days after mating and rats at postnatal day 19 (P19). Treatments were Cu-adequate (Cu +) and Cu-deficient (Cu −) diets with or without DOPS (1 mg/ml) in the drinking water. Mouse pups were killed at P14 and rats at P49. Mortality in Cu − pups was 46% and not significantly improved by DOPS, 39%. A repeat study with mice adding ascorbic acid in the water with DOPS showed no improvement. Compared to Cu + animals, Cu − animals were smaller, anemic and had a 92% reduction in liver Cu. DOPS treatment made no improvement to and in some cases exacerbated the Cu deficiency. Catecholamine levels measured in heart and brain by LCEC showed decreased NE levels and increased DA levels in Cu − animals compared to controls. DOPS treatment did not alter this pattern. Although DOPS was present in treated animal’s tissues, survival in mice and catecholamine levels in mice and rats were not altered by the 1 mg/ml dose of DOPS. PMID:16117185

Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans.

PubMed

Kohli, Utkarsh; Hahn, Maureen K; English, Brett A; Sofowora, Gbenga G; Muszkat, Mordechai; Li, Chun; Blakely, Randy D; Stein, C Michael; Kurnik, Daniel

2011-04-01

The presynaptic norepinephrine transporter (NET) mediates synaptic clearance and recycling of norepinephrine. NET-deficient transgenic mice have elevated blood pressure (BP), heart rate, and catecholamine concentrations. However, the in-vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown. We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50, and 75 W) in 145 healthy participants. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures. 44 and 58.9% of participants carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic BP during exercise and systolic BP-area under the curve were higher in carriers of variant NET alleles (P=0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-3081T compared with -182T/-3081A (all P<0.01). Diastolic BP during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P<0.01) and -3081T variants (P<0.05). NET genotypes were not associated with catecholamine concentrations or heart rate. Common genetic NET variants (-182C and -3081T) are associated with greater BP response to exercise in humans.

Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow.

PubMed

Rupp, H; Dhalla, K S; Dhalla, N S

1994-01-01

A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.

[Hereditary phaeochromocytoma in twins].

PubMed

Tóth, Géza; Patócs, Attila; Tóth, Miklós

2016-08-01

Phaeochromocytoma is a tumor of the catecholamine-producing cells of the adrenal gland. Extraadrenal phaeochromocytomas are frequently called paragangliomas. The majority of phaeochromocytomas are sporadic, however, about 25-30% are caused by genetic mutation. These tumor are frequently referred as hereditary phaeochromocytomas/paragangliomas. Their incidence increases continuously which can be attributed to availability of genetic examination and to the discovery of novel genes. The 47-year-old female patient underwent abdominal computed tomography which revealed bilateral adrenal gland enlargement. Abdominal magnetic resonance imaging, the 131-I- metaiodobenzylguanidine scintigraphy, urinary catecholamines and serum chomogranin A measurements confirmed the diagnosis of bilateral phaeochromocytomas. The genetically identical twin sister of the patient was also diagnosed with hormonally active bilateral phaechromocytoma, suggesting the genetic origin of phaeochromocytoma. Mutation screening confirmed a germline mutation of the transmembrane protein 127 tumorsupressor gene in both patients. Both patients underwent cortical-sparing adrenalectomy. The adrenal gland with the larger tumor was totally resected, while in the opposite side only the tumor was resected and a small part of the cortex was saved. After the operation urinary catecholamines and serum chromogranin A returned to normal in both patients. Adrenocortical deficiency was absent in the first patient, but her sister developed adrenal insufficiency requiring glucocorticoid replacement. To the best of the authors' knowledge phaeochromocytoma affecting twins has never been described earlier. Genetic examination performed in siblings confirmed the presence of the mutant gene through four generations. Orv. Hetil., 2016, 157(33), 1326-1330.

Phaeochromocytoma: diagnostic challenges for biochemical screening and diagnosis.

PubMed

Barron, Jeffrey

2010-08-01

The aim of this article is to provide knowledge of the origin of catecholamines and metabolites so that there can be an informed approach to the methods for biochemical screening for a possible phaeochromocytoma; The article includes a review of catecholamine and metadrenaline metabolism, with methods used in biochemical screening. In the adrenal medulla and a phaeochromocytoma, catecholamines continuously leak from chromaffin granules into the cytoplasm and are converted to metadrenalines. For a phaeochromocytoma to become biochemically detectable, metnoradrenaline secretion needs to rise fourfold, whereas noradrenaline secretion needs to rise 15-fold. The prevalence of a sporadic phaeochromocytoma is low; therefore false-positive results exceed true-positive results. Assay sensitivity is high because it is important not to miss a possible phaeochromocytoma. The use of urine or plasma fractionated metadrenalines as the first-line test has been recommended due to improved sensitivity. A negative result excludes a phaeochromocytoma. Only after a sporadic phaeochromocytoma has been diagnosed biochemically is it cost effective to request imaging. Sensitivities and specificities of the assays differ according to pre-test probabilities of the presence of a phaeochromocytoma, with hereditary and incidentalomas having a higher pre-test probability than sporadic phaeochromocytoma. In conclusion, in screening for a possible phaeochromocytoma, biochemical investigations should be completed first to exclude or establish the diagnosis. The preferred biochemical screening test is fractionated metadrenalines, including methoxytyramine so as not to miss dopamine-secreting tumours.

No Elevated Plasma Catecholamine Levels during Sleep in Newly Diagnosed, Untreated Hypertensives

PubMed Central

Rasch, Björn; Dodt, Christoph; Sayk, Friedhelm; Mölle, Matthias; Born, Jan

2011-01-01

The sympatho-adrenergic system is highly involved in regulating sleep, wake and arousal states, and abnormalities in this system are regarded as a key factor in the development and progression of arterial hypertension. While hypertension is associated with a hyperadrenergic state during wakefulness, the effect of hypertension on plasma-catecholamine levels during sleep is not yet known. Twelve young participants with newly diagnosed, untreated hypertension and twelve healthy controls slept for 7 hours in the sleep laboratory. Before and after sleep, subjects rested in a supine position for 3-h periods of wakefulness. We sampled blood at a fast rate (1/10 min) and monitored blood pressure and heart rate continuously. We show that plasma NE and E levels did not differ between hypertensives and normotensive during sleep as well as before and after sleep. Blood pressure was higher in hypertensives, reaching the largest group difference in the morning after sleep. Unlike in the normotensives, in the hypertensive participants the morning rise in blood pressure did not correlate with the rise in catecholamine levels at awakening. Our results suggest that hypertension in its early stages is not associated with a strong hyperadrenergic state during sleep. In showing a diminished control of blood pressure through sympatho-adrenergic signals in hypertensive participants, our data point towards a possible involvement of dysfunctional sleep-related blood pressure regulation in the development of hypertension. PMID:21695061

Types of aggressiveness and catecholamine response in essential hypertensives and healthy controls.

PubMed

Netter, P; Neuhäuser-Metternich, S

1991-01-01

Relationships between plasma catecholamine responses, and levels and types of aggression in hyper- and normotensives were investigated by analyses of data obtained in a large psychophysiological experiment on 97 hypertensives (EH) and 98 normotensives (CO) each. Subjects were divided according to levels (high vs low) and types (repressed vs manifest) of aggressiveness according to self rating questionnaire scores. Their plasma catecholamine responses to defined stressors indicating sympathetic arousability were compared by four factor analyses of covariance adjusting for age. Repressed aggression was significantly more frequent among male EH, whereas manifest aggression was significantly more frequent among the male COs. High as compared to low hostility was associated with significantly elevated values of plasma epinephrine in EH but not in CO. The immediate norepinephrine stress response was blunted but showed a delayed increase during the subsequent period of rest in high aggressives of both the EH and CO group, a pattern particularly pronounced in repressed aggressive hypertensives. Neither cardiovascular reactions nor speed of performance were observed to be substantially different in subjects of repressed and of manifest hostility. It was concluded that aggression in general is characterized by a delayed norepinephrine stress response and that an association with high epinephrine is typical for aggressiveness in hypertensives. Repressed hostility, however, does not produce a sympathomedullary pattern substantially different from that of manifest aggression thus casting doubt on the physiological significance of repression claimed by Alexander.

Magnesium sulphate attenuates arterial pressure increase during laparoscopic cholecystectomy.

PubMed

Jee, D; Lee, D; Yun, S; Lee, C

2009-10-01

Magnesium is well known to inhibit catecholamine release and attenuate vasopressin-stimulated vasoconstriction. We investigated whether i.v. magnesium sulphate attenuates the haemodynamic stress responses to pneumoperitoneum by changing neurohumoral responses during laparoscopic cholecystectomy. Thirty-two patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups; a control group was given saline, and a magnesium group received magnesium sulphate 50 mg kg(-1) immediately before pneumoperitoneum. Arterial pressure, heart rate, serum magnesium, plasma renin activity (PRA), and catecholamine, cortisol, and vasopressin levels were measured. Systolic and diastolic arterial pressures were greater in the control group (P<0.05) than in the magnesium group at 10, 20, and 30 min post-pneumoperitoneum. Norepinephrine or epinephrine levels [pg ml(-1), mean (SD)] were higher in the control group than in the magnesium group at 5 [211 (37) vs 138 (18)] or 10 min [59 (19) vs 39 (9)] post-pneumoperitoneum, respectively (P<0.05). In the control group, vasopressin levels [pg ml(-1), mean (SD)] were higher compared with the magnesium group at 5 [64 (18) vs 35 (9), P<0.01] and 10 min [65 (18) vs 47 (11), P<0.05] post-pneumoperitoneum. There were no significant differences between the groups in PRA and cortisol levels. I.V. magnesium sulphate before pneumoperitoneum attenuates arterial pressure increases during laparoscopic cholecystectomy. This attenuation is apparently related to reductions in the release of catecholamine, vasopressin, or both.

Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems

PubMed Central

Backman, L J; Andersson, G; Fong, G; Alfredson, H; Scott, A; Danielson, P

2013-01-01

The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research. PMID:22292987

(Study of the behavioral and biological effects of high intensity 60 Hz electric fields): Quarterly technical progress report No. 29

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orr, J.L.

1989-07-14

Activities this quarter involved all phases of the project plus a meeting of the Joint Committee in Tokyo. Detailed mapping of the exposure facility is scheduled to be completed during the week of August 14, 1989. Both electric and magnetic fields should be available for tests of the components of the tether and blood sampling system for the neuroendocrine pilot study in September 1989. The groups for the social behavior study are stabilizing appropriately. Details on the formation of the groups and their status has been provided. Dr. Coelho has included information related to aspects of the social experiment rangingmore » from age estimation in baboons through the cardiovascular consequences of psychosocial stress. In addition, a draft manuscript is included on the data from the previous experiments which describes the effects of 30 and 60 kV/m electric fields on the social behavior of baboons. Tests of the blood handling procedures and analysis methods have been completed. With the exception of the catecholamine analyses, the handling procedures and variability in replicate measurements are satisfactory. Logistic and practical considerations now weigh strongly against including the analysis of the blood samples for catecholamines. Preliminary tests indicate that a sampling procedure which will work for the other compounds is probably not satisfactory for the catecholamines.« less

Chronic stress effects on working memory: association with prefrontal cortical tyrosine hydroxylase.

PubMed

Lee, Young-A; Goto, Yukiori

2015-06-01

Chronic stress causes deficits in cognitive function including working memory, for which transmission of such catecholamines as dopamine and noradrenaline transmission in the prefrontal cortex (PFC) are crucial. Since catecholamine synthesis depends on the rate-limiting enzyme, tyrosine hydroxylase (TH), TH is thought to play an important role in PFC function. In this study, we found that two distinct population existed in Sprague-Dawley rats in terms of working memory capacity, one with higher working memory capacity, and the other with low capacity. This distinction of working memory capacity became apparent after rats were exposed to chronic stress. In addition, such working memory capacity and alterations of working memory function by chronic stress were associated with TH expression in the PFC. Copyright © 2015 Elsevier B.V. All rights reserved.

Recent advances in chromaffin cell biology: summing up the last International Symposium on Chromaffin Cell Biology.

PubMed

Cárdenas, Ana M

2004-01-01

The International Symposium on Chromaffin Cell Biology (ISCCB) brings together a group of approximately 150 scientists from around the world who meet every 2 years to discuss recent advances in our understanding of biogenesis and motion of secretory vesicles, synthesis, storage and release of secreted products (catecholamines, chromogranins, ATP), and mechanisms involving the excitation-secretion coupling, membrane ion channels, intracellular calcium homeostasis and exocytosis. The development of new technologies that allow an accurate measurement of catecholamines, vesicle motion, exocytosis, etc. are also analyzed. The 12th ISCCB, organized by Ricardo Borges, took place on September 20-26, 2003, in La Palma, Canary Islands, Spain. In this article we describe the most recent and significant contributions to the 12th ISCCB.

The coexistence of renal artery stenosis and pheochromocytoma.

PubMed Central

Hill, F S; Jander, H P; Murad, T; Diethelm, A G

1983-01-01

The coexistence of renal artery stenosis and pheochromocytoma has been recognized since 1958 and a total of 36 patients reported. This article provides an additional patient with an extra adrenal pheochromocytoma and fibrous bands constricting the left renal artery. Hypertension was confirmed to occur from both excess catecholamine production and hyperreninemia from the left kidney. Surgical removal of the functioning paraganglioma and correction of the renal artery stenosis restored the postoperative plasma catecholamine, renin, and blood pressure to normal. A literature review confirmed the coexistence of these two lesions but failed to provide a common etiology to explain the pathophysiology encountered. However, when the two diseases occur simultaneously, both must be diagnosed accurately and treated in a definitive manner. Images Figs. 1a and b. Figs. 2a and b. PMID:6830355

Effects of water immersion on plasma catecholamines in normal humans

NASA Technical Reports Server (NTRS)

Epstein, M.; Johnson, G.; Denunzio, A. G.

1983-01-01

An investigation was conducted in order to determine whether water immersion to the neck (NI) alters plasma catecholamines in normal humans. Eight normal subjects were studied during a seated control study (C) and during 4 hr of NI, and the levels of norepinephrine (NE) and epinephrine (E) as determined by radioenzymatic assay were measured hourly. Results show that despite the induction of a marked natriuresis and diuresis indicating significant central hypervolemia, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 hr. In addition, the diuresis and natriuresis was found to vary independently of NE. These results indicate that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.

Urine Metanephrines

MedlinePlus

... Not Listed? Not Listed? 5-HIAA 17-Hydroxyprogesterone Acetaminophen Acetylcholine Receptor (AChR) Antibody Acid-Fast Bacillus (AFB) ... the rate at which the body uses energy ( metabolism ). After completing their actions, the catecholamines are broken ...

Catecholamine blood test

MedlinePlus

... out certain rare tumors, such as pheochromocytoma or neuroblastoma . It may also be done in patients with ... Ganglioblastoma (very rare tumor) Ganglioneuroma (very rare tumor) Neuroblastoma (rare tumor) Pheochromocytoma (rare tumor) Severe stress Additional ...

Emotional, neurohormonal, and hemodynamic responses to mental stress in Tako-Tsubo cardiomyopathy.

PubMed

Smeijers, Loes; Szabó, Balázs M; van Dammen, Lotte; Wonnink, Wally; Jakobs, Bernadette S; Bosch, Jos A; Kop, Willem J

2015-06-01

Tako-Tsubo cardiomyopathy (TTC) is characterized by apical ballooning of the left ventricle and symptoms and signs mimicking acute myocardial infarction. The high catecholamine levels in the acute phase of TTC and common emotional triggers suggest a dysregulated stress response system. This study examined whether patients with TTC show exaggerated emotional, neurohormonal, and hemodynamic responses to mental stress. Patients with TTC (n = 18; mean age 68.3 ± 11.7, 78% women) and 2 comparison groups (healthy controls, n = 19; mean age 60.0 ± 7.6, 68% women; chronic heart failure, n = 19; mean age 68.8 ± 10.1, 68% women) performed a structured mental stress task (anger recall and mental arithmetic) and low-grade exercise with repeated assessments of negative emotions, neurohormones (catecholamines: norepinephrine, epinephrine, dopamine, hypothalamic-pituitary-adrenal axis hormones: adrenocorticotropic hormone [ACTH], cortisol), echocardiography, blood pressure, and heart rate. TTC was associated with higher norepinephrine (520.7 ± 125.5 vs 407.9 ± 155.3 pg/ml, p = 0.021) and dopamine (16.2 ± 10.3 vs 10.3 ± 3.9 pg/ml, p = 0.027) levels during mental stress and relatively low emotional arousal (p <0.05) compared with healthy controls. During exercise, norepinephrine (511.3 ± 167.1 vs 394.4 ± 124.3 pg/ml, p = 0.037) and dopamine (17.3 ± 10.0 vs 10.8 ± 4.1 pg/ml, p = 0.017) levels were also significantly higher in patients with TTC compared with healthy controls. In conclusion, catecholamine levels during mental stress and exercise were elevated in TTC compared with healthy controls. No evidence was found for a dysregulated hypothalamic-pituitary-adrenal axis or hemodynamic responses. Patients with TTC showed blunted emotional arousal to mental stress. This study suggests that catecholamine hyper-reactivity and not emotional hyper-reactivity to stress is likely to play a role in myocardial vulnerability in TTC. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective stimulation of catecholamine release from bovine adrenal chromaffin cells by an ionotropic purinergic receptor sensitive to 2-methylthio ATP.

PubMed

Tomé, Angelo R; Castro, Enrique; Santos, Rosa M; Rosário, Luís M

2007-06-20

2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+ influx and evokes catecholamine release from adrenal chromaffin cells. These cells express P2Y and P2X (ionotropic) purinoceptors, with the latter providing an important Ca2+ influx pathway. Using single cell calcium imaging techniques, we have determined whether 2-MeSATP might be a specific P2X receptor agonist in bovine chromaffin cells and assessed the relative role of P2X and P2Y receptors on catecholamine secretion from these cells. ATP raised the [Ca2+]i in ~50% of the cells. Removing extracellular Ca2+ suppressed the [Ca2+]i-raising ability of 2-MeSATP, observed in ~40% of the ATP-sensitive cells. This indicates that 2-MeSATP behaves as a specific ionotropic purinoceptor agonist in bovine chromaffin cells. The 2-MeSATP-induced [Ca2+]i-rises were suppressed by PPADS. UTP raised the [Ca2+]i in ~40% of the ATP-sensitive cells, indicating that these expressed Ca2+-mobilizing P2Y receptors. UTP-sensitive receptors may not be the only P2Y receptors present, as suggested by the observation that ~20% of the ATP-sensitive pool did not respond to either 2-MeSATP or UTP. The average sizes of the ATP- and 2-MeSATP-evoked [Ca2+]i responses were identical in UTP-insensitive cells. 2-MeSATP stimulated Ca2+ influx and evoked catecholamine release, whereas UTP elicited Ca2+ release from intracellular stores but did not evoke secretion. 2-MeSATP-induced secretion was strongly inhibited by Cd2+ and suppressed by extracellular Ca2+ or Na+ removal. TTX inhibited 2-MeSATP-evoked secretion by ~20%. 2-MeSATP is a specific P2X purinoceptor agonist and a potent secretagogue in bovine chromaffin cells. Activation of 2-MeSATP-sensitive receptors stimulates Ca2+ influx mainly via voltage-sensitive Ca2+ channels. For the most part, these are activated by the depolarization brought about by Na+ influx across P2X receptor pores.

In vitro Catecholamine Exposure Produces Variable Effects on the B7 Costimulatory Pathway in Human Monocytic Cells

NASA Technical Reports Server (NTRS)

Salicru, A. N.; Crucian, B.; Sams, Clarence; Actor, J. K.; Marshall, G. D., Jr.

2006-01-01

Catecholamines have been associated with immunomodulation of the adaptive immune system towards a Th2 response in vitro. We therefore examined the role of in vitro epinephrine (EPI) and norepinephrine (NE) exposure on the B7 costimulatory expression of antigen presenting cells (APC) from human monocytic cell lines and human peripheral blood mononuclear cells (PBMC). THP1 monocytic cells and CD14+ cells from normal human PBMC were stimulated with lipopolysaccharide (LPS) and incubated with physiologic stress levels (10(exp -6) - 10(exp -8)M) of EPI or NE for 24 hours. Cells were subsequently stained with CD80 FITC, CD86 PE, and CD14 PC5 antibodies and analyzed by flow cytometry for changes in fluorescence and mean fluorescence intensity (MFI). Exposure of THP1 to EPI in vitro at concentrations of 10(exp -6), 10(exp -7) and 10(exp -8)M significantly decreased mean CD80 from 42 plus or minus 0.7% to 11 plus or minus 0.44%, 19.1 plus or minus 2.0%, and 30.7 plus or minus 2.1% expression, respectively (p less than 0.01). In addition, CD86 expression increased with EPI at 10(exp -6), 10(exp -7) and 10(exp -8) M from 9.2 plus or minus 0.52% to 41 plus or minus 3.8%, 26.4 plus or minus 1.9%, and 15.74 plus or minus 1.8% expression, respectively (p less than 0.01). Similar results for mean CD80 and CD86 percent expression were observed for CD14+ cells from PBMC with a sample size of N = 6 and for NE when substituted for EPI. The data show that in vitro exposure to catecholamines significantly decreases %CD86 expression and significantly increases %CD86 expression in THP1 cells and human CD14+ APC. Previous studies have suggested an association between increased CD86 expression and TH2 activity. Thus, these data suggest that immunomodulation by catecholamines results in part by the variable effects of the B7 costimulatory pathway in APC.

The effects of C-type natriuretic peptide on catecholamine release in the pacific spiny dogfish (Squalus acanthias).

PubMed

Montpetit, C J; McKendry, J; Perry, S F

2001-08-01

The interaction between homologous C-type natriuretic peptide (dfCNP) and catecholamine release in cardiovascular control was assessed in the marine dogfish (Squalus acanthias). This was accomplished by evaluation of the dynamics of the dfCNP-elicited secretion of catecholamines in situ and in vivo. With an in situ saline-perfused postcardinal sinus preparation, it was demonstrated that perfusion with saline containing dfCNP (10(-9) mol x L(-1)) did not affect the secretion of either noradrenaline or adrenaline. However, the presence of dfCNP in the perfusate significantly enhanced carbachol-evoked secretion of noradrenaline. In vivo, intravascular injection of dfCNP (10(-9) mol x kg(-1)) caused a biphasic pressor-depressor response consisting of a brief increase in caudal artery blood pressure (P(CA)) followed by a prolonged reduction in P(CA). Furthermore, although systemic resistance initially increased, it was subsequently maintained at baseline values in the face of persistent decreases in both P(CA) and cardiac output. Bolus injection of dfCNP elicited significant increases in plasma noradrenaline levels that peaked within 10 min; plasma adrenaline levels were unaffected. The release of noradrenaline elicited by dfCNP was unaffected by prior blockade of the renin-angiotensin system (RAS) (with the angiotensin converting enzyme inhibitor lisinopril) or by pretreatment with the nicotinic receptor blocker hexamethonium. The delayed decrease in P(CA) was not observed in the hexamethonium-treated fish. Prior blockade of beta-adrenoreceptors (with sotalol) or alpha-adrenoreceptors (with prazosin) either significantly reduced (sotalol) or abolished (prazosin) the increase in plasma noradrenaline levels after dfCNP injection. The results of this investigation demonstrate that the elevation of plasma noradrenaline levels observed in vivo following dfCNP injection is not caused by a direct effect of dfCNP on catecholamine secretion from axillary body chromaffin cells. Furthermore, the dfCNP-mediated increase of plasma noradrenaline appears to be unrelated to changes in P(CA) and is insensitive to blockade of the RAS or nicotinic receptors. However, stimulation of adrenergic receptors, in particular the alpha-adrenoreceptors, appears to be a key mechanism underlying the dfCNP-elicited secretion of noradrenaline. Copyright 2001 Academic Press.

Change in energy expenditure and brain and adrenal content of catecholamines in rats during muscular loading and hypokinesia

NASA Technical Reports Server (NTRS)

Rozanova, V. D.; Savkiv, T. G.; Khodorova, N. A.

1980-01-01

In male 1-7 month old rats, the growth and the protein content of skeletal muscles were higher than in female rats while the O2 consumption and the heart rate were lower. This is combined with reduction of the thyroid gland weight and of catecholamine content in adrenals at the age of 7 months. The development of male and female rats (1-7 month) under conditions of systematic muscular loads increases the growth tempo and protein of skeletal muscles and intensifies the degree of reduction of energy expenditure and the heart rate. This is accomplished by the greater reduction of relative weight of the thyroid gland and, at the age of 7 months, by reduction of the noradrenaline content in the brainstem. Hypodynamic conditions have the exact opposite effect.

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

PubMed

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects

NASA Astrophysics Data System (ADS)

Vatsadze, S. Z.; Eremina, O. E.; Veselova, I. A.; Kalmykov, S. N.; Nenajdenko, V. G.

2018-04-01

The pathogenesis of many socially significant diseases such as neurodegenerative dementias and neuroendocrine tumours involves imbalance of neurotransmitters. Among the known neuroimaging methods, positron emission tomography (PET) is the most perfect and informative technique for diagnosing these diseases. The potential of PET is largely determined by the inventory of available radiopharmaceuticals, that is, biologically active molecules containing short-lived nuclides with positron decay. This review gives a systematic account of the application of fluorine-18-labelled catecholamine type radiopharmaceuticals in clinical investigations of the sympathetic and central nervous systems. The methods for the synthesis of these agents and existing problems are considered. The material is arranged according to the mechanisms of reactions that underlie the synthetic approaches: electrophilic, nucleophilic and metal-catalyzed reactions. The bibliography includes 198 references.

Aging and unusual catecholamine-containing structures in the mouse brain.

PubMed

Masuoka, D T; Jonsson, G; Finch, C E

1979-06-22

Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.

Permanent alterations in catecholamine concentrations in discrete areas of brain in the offspring of rats treated with methylamphetamine and chlorpromazine

PubMed Central

Tonge, Sally R.

1973-01-01

Methylamphetamine hydrochloride (80 mg/l.) and/or chlorpromazine hydrochloride (200 mg/l.) have been administered in the drinking water of female Wistar rats during pregnancy and suckling. The offspring were weaned at 21 days and thereafter received no drugs. Nine months later, male offspring were killed and noradrenaline and normetanephrine concentrations were determined in eight discrete areas of the brains: neocortex, hippocampus, striatum, thalamus, hypothalamus, corpora quadrigemina, pons/medulla, and amygdala region. Both drugs appeared to have permanently altered catecholamine concentrations in several areas of the brain. There was evidence of antagonism between the effects of the two drugs in the hippocampus, striatum, thalamus, and corpora quadrigemina, where the individual drugs produced altered noradrenaline concentrations but a combination of the two had no effect. PMID:4722052

Tako-Tsubo cardiomyopathy presenting with cardiogenic shock successfully treated with milrinone: a case report.

PubMed

Doyen, Denis; Dellamonica, Jean; Moceri, Pamela; Moschietto, Sébastien; Hyvernat, Hervé; Ferrari, Emile; Bernardin, Gilles

2014-01-01

We report the case of a middle age patient presenting with Tako-Tsubo cardiomyopathy (TTC) complicated by cardiogenic shock that was successfully handled with milrinone. A 64-year old man presented with cardiogenic shock after benzodiazepine and alcohol intoxication. A slight elevation of troponin and typical left ventricular ballooning without coronary lesions suggested TTC. Within a few hours milrinone infusion normalized the cardiac index. TTC is responsible for severe transient left ventricular dysfunction occurring after physical or psychological stress. The major pathophysiological mechanism involved is disproportionate catecholamine secretion, which may stun the myocardium. We considered if treatment of this unique physiopathology with catecholamines could be dangerous in these patients and if alternative inotropes such as milrinone should be preferred. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Inhibition of radioemesis by disruption of catecholamines in dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

1981-03-01

Dogs were treated 30 min to 1 h before x irradiation with ..cap alpha..-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, ..cap alpha..-Methyl-p-tyrosine caused no significantmore » changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons.« less

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response.

PubMed

Eng, Jason W-L; Kokolus, Kathleen M; Reed, Chelsey B; Hylander, Bonnie L; Ma, Wen W; Repasky, Elizabeth A

2014-11-01

Long conserved mechanisms maintain homeostasis in living creatures in response to a variety of stresses. However, continuous exposure to stress can result in unabated production of stress hormones, especially catecholamines, which can have detrimental health effects. While the long-term effects of chronic stress have well-known physiological consequences, recent discoveries have revealed that stress may affect therapeutic efficacy in cancer. Growing epidemiological evidence reveals strong correlations between progression-free and long-term survival and β-blocker usage in cancer patients. In this review, we summarize the current understanding of how the catecholamines, epinephrine and norepinephrine, affect cancer cell survival and tumor progression. We also highlight new data exploring the potential contributions of stress to immunosuppression in the tumor microenvironment and the implications of these findings for the efficacy of immunotherapies.

Genetic Variation in the Presynaptic Norepinephrine Transporter is Associated with Blood Pressure Responses to Exercise in Healthy Humans

PubMed Central

Kohli, Utkarsh; Hahn, Maureen K.; English, Brett A.; Sofowora, Gbenga G.; Muszkat, Mordechai; Li, Chun; Blakely, Randy D.; Stein, C. Michael; Kurnik, Daniel

2011-01-01

Background The presynaptic norepinephrine (NE) transporter (NET) mediates synaptic clearance and recycling of NE. NET-deficient transgenic mice have elevated blood pressure, heart rate, and catecholamine concentrations. However, the in vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown. Methods We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50 and 75 W) in 145 healthy subjects. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures. Results 44% and 58.9% of subjects carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic blood pressure (SBP) during exercise and SBP area-under-the-curve were higher in carriers of variant NET alleles (P=0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-081T compared to -82T/-3081A (all P<0.01). Diastolic blood pressure (DBP) during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P<0.01) and -081T (P< 0.05). NET genotypes were not associated with catecholamine concentrations or heart rate. Conclusion Common genetic NET variants (-182C and -081T) are associated with greater blood pressure response to exercise in humans. PMID:21412203

Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy

PubMed Central

Yipintsoi, Tada; Kroll, Keith

2015-01-01

Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5–1 ml·g−1·min−1 and increased to 2–3 ml·g−1·min−1 with catecholamine infusion and to ∼4 ml·g−1·min−1 with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1–0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, “tracking” closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states. PMID:26589329

Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

PubMed

Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

2016-02-01

Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states. Copyright © 2016 the American Physiological Society.

Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

PubMed

Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; Del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

2016-05-01

Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonhydrolytic sol-gel approach to facile creation of surface-bonded zirconia organic-inorganic hybrid coatings for sample preparation. Ι. Capillary microextraction of catecholamine neurotransmitters.

PubMed

Alhendal, Abdullah; Mengis, Stephanie; Matthews, Jacob; Malik, Abdul

2016-10-14

Nonhydrolytic sol-gel (NHSG) route was used for the creation of novel zirconia-polypropylene oxide (ZrO 2 -PPO) sol-gel hybrid sorbents in the form of surface coatings for the extraction and preconcentration of catecholamine neurotransmitters and molecules structurally related to their deaminated metabolites. In comparison to other sorbents made of inorganic transition metal oxides, the presented hybrid organic-inorganic sorbents facilitated reversible sorption properties that allowed for efficient desorption of the extracted analytes by LC-MS compatible mobile phases. The presented sol-gel hybrid sorbents effectively overcame the major drawbacks of traditional silica- or polymer-based sorbents by providing superior pH stability (pH range: 0-14), and a variety of intermolecular interactions. Nonaqueous sol-gel treatment of PPO with ZrCl 4 was employed for the derivatization of the terminal hydroxyl groups on PPO, providing zirconium trichloride-containing end groups characterized by enhanced sol-gel reactivity. NHSG ZrO 2 -PPO sorbent provided excellent microextraction performance for catecholamines, low detection limits (5.6-9.6pM), high run-to-run reproducibility (RSD 0.6-5.1%), high desorption efficiency (95.0-99.5%) and high enrichment factors (∼1480-2650) for dopamine and epinephrine, respectively, extracted from synthetic urine samples. The presented sol-gel sorbents provided effective alternative to conventional extraction media providing unique physicochemical characteristics and excellent extraction capability. Copyright © 2016 Elsevier B.V. All rights reserved.

Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management.

PubMed

Eisenhofer, Graeme; Rivers, Graham; Rosas, Alejandro L; Quezado, Zena; Manger, William M; Pacak, Karel

2007-01-01

The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D(2) receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications.

Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ

PubMed Central

Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

2014-01-01

This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. PMID:25032843

Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction

PubMed Central

Kim, Nahyun; Hughes, Tonda L.; Park, Chang G.; Quinn, Laurie

2016-01-01

Abstract The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ2-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t =−6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents. PMID:26849530

Increased release of norepinephrine and dopamine from canine kidney during bilateral carotid occlusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, T.; Hjemdahl, P.; DiBona, G.F.

1987-02-01

The renal overflow of norepinephrine (NE) and dopamine (DA) to plasma from the innervated kidney was studied at rest and during sympathetic nervous system activation by bilateral carotid artery occlusion (BCO) in vagotomized dogs under barbiturate or barbiturate/nitrous oxide anesthesia. BCO elevated arterial pressure and the arterial plasma concentration of NE, DA, and epinephrine (Epi). Renal vascular resistance (renal arterial pressure kept constant) increased by 15 +/- 7% and the net renal venous outflows (renal veno-arterial concentration difference x renal plasma flow) of NE and DA were enhanced. To obtain more correct estimates of the renal contribution to the renalmore » venous catecholamine outflow, they corrected for the renal extraction of arterial catecholamines, assessed as the extractions of (/sup 3/H)NE, (/sup 3/H)DA, or endogenous Epi. The (/sup 3/H)NE corrected renal NE overflow to plasma increased from 144 +/- 40 to 243 +/- 64 pmol-min/sup -1/ during BCO, which, when compared with a previous study of the (/sup 3/H)NE corrected renal NE overflow to plasma evoked by electrical renal nerve stimulation, corresponds to a 40% increase in nerve impulse frequency from approx. 0.6 Hz. If the renal catecholamine extraction was not taken into account the effect of BCO was underestimated. The renal DA overflow to plasma was about one-fifth of the NE overflow both at rest and during BCO, indicating that there was no preferential activation of noradrenergic or putative dopaminergic nerves by BCO.« less

Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder.

PubMed

Lin, Chen-Cheng; Tung, Che-Se; Lin, Pin-Hsuan; Huang, Chuen-Lin; Liu, Yia-Ping

2016-09-01

Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

PubMed Central

2016-01-01

As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:22297542

Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

PubMed Central

2017-01-01

As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:21615193

Oral administration of D-aspartate, but not L-aspartate, depresses rectal temperature and alters plasma metabolites in chicks.

PubMed

Erwan, Edi; Chowdhury, Vishwajit Sur; Nagasawa, Mao; Goda, Ryosei; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

2014-07-25

L-Aspartate (L-Asp) and D-aspartate (D-Asp) are physiologically important amino acids in mammals and birds. However, the functions of these amino acids have not yet been fully understood. In this study, we therefore examined the effects of L-Asp and D-Asp in terms of regulating body temperature, plasma metabolites and catecholamines in chicks. Chicks were first orally administered with different doses (0, 3.75, 7.5 and 15 mmol/kg body weight) of L- or D-Asp to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period. Oral administration of D-Asp, but not of L-Asp, linearly decreased the rectal temperature in chicks. Importantly, orally administered D-Asp led to a significant reduction in body temperature in chicks even under high ambient temperature (HT) conditions. However, centrally administered D-Asp did not significantly influence the body temperature in chicks. As for plasma metabolites and catecholamines, orally administered D-Asp led to decreased triacylglycerol and uric acid concentrations and increased glucose and chlorine concentrations but did not alter plasma catecholamines. These results suggest that oral administration of D-Asp may play a potent role in reducing body temperature under both normal and HT conditions. The alteration of plasma metabolites further indicates that D-Asp may contribute to the regulation of metabolic activity in chicks. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.

PubMed

Jung, Ye-Ha; Kang, Do-Hyung; Jang, Joon Hwan; Park, Hye Yoon; Byun, Min Soo; Kwon, Soo Jin; Jang, Go-Eun; Lee, Ul Soon; An, Seung Chan; Kwon, Jun Soo

2010-07-26

This study was designed to assess the association between stress, positive affect and catecholamine levels in meditation and control groups. The meditation group consisted of 67 subjects who regularly engaged in mind-body training of "Brain-Wave Vibration" and the control group consisted of 57 healthy subjects. Plasma catecholamine (norepinephrine (NE), epinephrine (E), and dopamine (DA)) levels were measured, and a modified form of the Stress Response Inventory (SRI-MF) and the Positive Affect and Negative Affect Scale (PANAS) were administered. The meditation group showed higher scores on positive affect (p=.019) and lower scores on stress (p<.001) compared with the control group. Plasma DA levels were also higher in the meditation (p=.031) than in the control group. The control group demonstrated a negative correlation between stress and positive affects (r=-.408, p=.002), whereas this correlation was not observed in the meditation group. The control group showed positive correlations between somatization and NE/E (r=.267, p=.045) and DA/E (r=.271, p=.042) ratios, whereas these correlations did not emerge in the meditation group. In conclusion, these results suggest that meditation as mind-body training is associated with lower stress, higher positive affect and higher plasma DA levels when comparing the meditation group with the control group. Thus, mind-body training may influence stress, positive affect and the sympathetic nervous system including DA activity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Alcohol and malnutrition in the pathogenesis of experimental alcoholic cardiomyopathy.

PubMed

Rossi, M A

1980-02-01

In this study, the morphology and the catecholamine levels of the myocardium in both well-nourished and malnourished alcohol-fed rats were examined. Alcohol has been administered to rats for 16 weeks. Rats fed a diet containing alcohol corresponding to 40 per cent. of total calorific intake and inadequate amounts of calories and nutrients developed morphological changes in the heart, while the controls did not. In addition, an increase in cardiac noradrenaline concentration and heart: body weight ratio could be observed. There were no differences in myocardial morphology and catecholamine concentration between well-nourished rats fed alcohol as 35 per cent. of the calorific intake and pair-fed controls. A dispute exists about whether alcohol is directly toxic to the heart or indirectly injurious due to associated dietary deficiency. The present results, taken together, make the theory of cardiotoxicity of alcohol an unlikely one, at least in the case of the rat; and they offer considerable support for the hypothesis that the association between chronic consumption of alcoholic beverages and cardiomyopathy is a result of a primary multifactorial nutritional deficiency, resulting from displacement of nutrient-associated calories by the "empty" calories--devoid of protein, vitamins, and minerals--of alcohol, and/or a secondary nutritional deficiency due to injurious effects of alcohol on the liver, pancreas and intestine. It is suggested that continued exposure to high levels of catecholamine, directly related to malnutrition, may play a role in the development of myocardial pathology.

Catecholamines, Plasma and Urine Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Von Hippel-Lindau Syndrome

MedlinePlus

... examination to look for retinal tumors, beginning around age 2 Yearly physical examination Yearly blood test and/or 24-hour urine test to screen for elevated catecholamines, beginning around age 5 Yearly abdominal ultrasound to look at the ...

ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

PubMed

Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

1999-01-01

The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

The sympathetic nervous system and the physiologic consequences of spaceflight: a hypothesis

NASA Technical Reports Server (NTRS)

Robertson, D.; Convertino, V. A.; Vernikos, J.

1994-01-01

Many of the physiologic consequences of weightlessness and the cardiovascular abnormalities on return from space could be due, at least in part, to alterations in the regulation of the autonomic nervous system. In this article, the authors review the rationale and evidence for an autonomic mediation of diverse changes that occur with spaceflight, including the anemia and hypovolemia of weightlessness and the tachycardia and orthostatic intolerance on return from space. This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). Both groups exhibit the symptoms mentioned. The increasing evidence that autonomic mechanisms underlie many of the physiologic consequences of weightlessness suggests that new pharmacologic approaches (such as administration of beta-blockers and/or sympathomimetic amines) based on these findings may attenuate these unwanted effects.

[Comparative study on the effect of antiatherosclerotic diet enriched with polyunsaturated omega-3 fatty acids of plant and animal origin on the level of natural antibodies against catecholamines in patients with cardiovascular diseases].

PubMed

Pogozheva, A V; Rozanova, I A; Miagkova, M A; Sorokovoĭ, K V; Panchenko, O N; Trubacheva, Zh N

1998-01-01

The levels of natural antibodies against catecholamines in 138 patients with cardiovascular diseases was studied and the comparative analysis of influence of antiatherosclerotic diets with different origin of PUFA omega-3 on dynamic of these parameters was made. For the first time discovered universal action of diets with PUFA omega-3 vegetable and animal origin on parameters of humoral immunity: in case of primary excess of norm of the contents of natural antibodies to adrenaline, noradrenaline and dopamine as a result of treatment these parameters were reduced or did not change; and at is primary a low their level--parameters increased in most cases. The greatest immunocorrection effect was rendered by diet, enriched PUFA omega-3 of freshwater fishes fat.

Development of the larval nervous system of the sand dollar, Dendraster excentricus.

PubMed

Burke, R D

1983-01-01

Transformation of the gastrula to the pluteus includes development of the ability of the larva to control the direction of ciliary beat and coordinate activities of the ciliary band with activities of the esophageal muscles (48-60 h, 15 degrees C). Glyoxylic acid-induced fluorescence shows several cells of the animal plate to contain catecholamines in the 36-h gastrula. As the ectoderm thickens to form the ciliary band (36 48 h), the catecholamine-containing cells increase in number and occur dispersed throughout the band. Tissues with the ultrastructural characteristics of nerves first became apparent associated with the ciliary band in 60-h larvae. The coincident development of coordinated behaviour and the appearance of cells with ultrastructural and histochemical characteristics of nerves suggests that the larval nervous system is derived at least in part from cells of the animal plate and develops in association with the ciliary bands.

Stress hyperglycaemia as a result of a catecholamine producing tumour in an infant.

PubMed

de Grauw, Anne Mariëtte; Mul, Dick; van Noesel, Max M; Buddingh, Emilie P

2015-09-04

Hyperglycaemia commonly occurs in children presenting at the emergency department. In the absence of diabetic symptoms, this stress-related hyperglycaemia is considered a benign condition. We present a malignant cause of hyperglycaemia in an 11-month-old girl with concomitant symptoms of a neuroendocrine malignancy. One month earlier, she had undergone an episode of stress-related hyperglycaemia concurrent with fever during an upper respiratory tract infection. Current glucose level was 234 mg/dL (13 mmol/L) and the glycosylated haemoglobin level was 44 mmol/mol (6.2%) without metabolic acidosis. We observed periods of hyperglycaemia, sweating, flushing, hypertension and tachypnoea. Urinalysis showed high amounts of catecholamine intermediates. Abdominal ultrasound revealed a mass originating in the right adrenal gland. Histology confirmed the diagnosis of neuroblastoma. Hyperglycaemia in this patient was the first presenting symptom of a metabolically active neuroblastoma. 2015 BMJ Publishing Group Ltd.

Changes of catecholamine excretion during long-duration confinement.

PubMed

Kraft, N; Inoue, N; Ohshima, H; Sekiguchi, C

2002-06-01

Simulation studies have become the main source of data about small group interactions during prolonged isolation, from which it should be possible to anticipate crew problems during actual space missions. International Space Station (ISS) astronauts and cosmonauts will form one international crew, although living in different national modules. They will have joint flight protocols, and at the same time, fulfill a number of different tasks in accord with their national flight programs. Consistent with these concepts, we studied two simultaneously functioning groups in a simulation of ISS flight. The objective of this study was to investigate physiological parameters (such as catecholamine excretions) related to long-duration confinement in the hermetic chamber, simulating International Space Station flight conditions. We also planned to evaluate the relationship between epinephrine/norepinephrine with group dynamics and social events to predict unfavorable changes in health and work capability of the subjects related to psychological interaction in the isolation chamber.

Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement

NASA Technical Reports Server (NTRS)

Gvishiani, G. S.; Kobakhidze, N. G.

1980-01-01

Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1: implications for Parkinson's disease and protection by polyphenols.

PubMed

Vauzour, David; Ravaioli, Giulia; Vafeiadou, Katerina; Rodriguez-Mateos, Ana; Angeloni, Cristina; Spencer, Jeremy P E

2008-08-15

Mechanisms of nigral cell injury in Parkinson's disease remain unclear, although a combination of increased oxidative stress, the formation of catecholamine-quinones and the subsequent formation of neurotoxic cysteinyl-catecholamine conjugates may contribute. In the present study, peroxynitrite was observed to generate both 2-S- and 5-S-cysteinyl-dopamine and a dihydrobenzothiazine species, DHBT-1, following the reaction of dopamine with l-cysteine. The formation of 5-S-cysteinyl-dopamine and DHBT-1 in the presence of peroxynitrite induced significant neuronal injury. Pre-treatment of cortical neurons with pelargonidin, quercetin, hesperetin, caffeic acid, the 4'-O-Me derivatives of catechin and epicatechin (0.1-3.0 microM) resulted in concentration dependant protection against 5-S-cysteinyl-dopamine-induced neurotoxicity. These data suggest that polyphenols may protect against neuronal injury induced by endogenous neurotoxins relevant to the aetiology of the Parkinson disease.

Clozapine response and plasma catecholamines and their metabolites.

PubMed

Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

1993-02-01

The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

Pheochromocytoma presenting as an acute coronary syndrome complicated by acute heart failure: The challenge of a great mimic.

PubMed

Sanna, Giuseppe Damiano; Talanas, Giuseppe; Fiore, Giuseppina; Canu, Antonella; Terrosu, Pierfranco

2016-10-01

Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical presentation. The serious and potentially lethal cardiovascular complications of these tumors are related to the effects of secreted catecholamines. We describe a case of a 50-year-old woman urgently admitted to our hospital because of symptoms and clinical and instrumental findings consistent with an acute coronary syndrome complicated by acute heart failure. Urgent coronary angiography showed normal coronary arteries. During her hospital stay, the recurrence of episodes characterized by a sudden increase in blood pressure, cold sweating, and nausea allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by elevated levels of urinary catecholamines and by the finding of a left adrenal mass on magnetic resonance imaging. The patient underwent left adrenalectomy. Therefore, the initial diagnosis was critically reappraised and reviewed as a cardiac manifestation of a pheochromocytoma during catecholaminergic crisis.

A case of suicide by self-injection of adrenaline.

PubMed

Palmiere, Cristian; Bévalot, Fabien; Malicier, Daniel; Grouzmann, Eric; Fracasso, Tony; Fanton, Laurent

2015-09-01

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Piezoelectric detection of ion pairs between sulphonate and catecholamines for flow injection analysis of pharmaceutical preparations.

PubMed

Mo, Z; Long, X; Zhang, M

1999-03-01

Fundamentals of ion-pair flow injection with piezoelectric detection were investigated experimentally and theoretically for the adsorption of dodecyl phenylsulfonate and interfacial ion-pair formation with epinephrine and l-dopa on silver electrode of quartz crystal microbalance. The influences of sulfonate concentration and operating parameters on the frequency response were demonstrated and provided the possibility for the discriminating determination of mixtures. The selected system of ion-pair flow injection with piezoelectric detection was applied to the determination of epinephrine and l-dopa. Calibration curves were linear in ranges 4.00-850 and 3.50-730 mug ml(-1), with detection limits of 1.22 and 1.05 mug ml(-1) and sampling frequencies of 120 samples h(-1), for epinephrine and l-dopa, respectively. The method has been satisfactorily applied to the determination of catecholamines in pharmaceutical preparations.

Conformational reduction of DOPA in the gas phase studied by laser desorption supersonic jet laser spectroscopy.

PubMed

Ishiuchi, Shun-ichi; Mitsuda, Haruhiko; Asakawa, Toshiro; Miyazaki, Mitsuhiko; Fujii, Masaaki

2011-05-07

The conformational reduction in catecholamine neurotransmitters was studied by resonance enhanced multi photon ionization (REMPI), ultraviolet-ultraviolet (UV-UV) hole burning and infrared (IR) dip spectroscopy with applying a laser desorption supersonic jet technique to DOPA, which is one of the catecholamine neurotransmitters and has one more phenolic OH group than tyrosine. It is concluded that DOPA has a single observable conformer in the gas phase at low temperature. Quantum chemical calculations at several levels with or without the dispersion correction were also carried out to study stable conformations. From the comparison between the computational IR spectra and the experimental ones, the most stable structure was determined. It is strongly suggested that the conformational reduction is caused by electrostatic interactions, such as a dipole-dipole interaction, between the chain and OH groups. This journal is © the Owner Societies 2011

Catecholaminergic challenge uncovers distinct Pavlovian and instrumental mechanisms of motivated (in)action.

PubMed

Swart, Jennifer C; Froböse, Monja I; Cook, Jennifer L; Geurts, Dirk Em; Frank, Michael J; Cools, Roshan; den Ouden, Hanneke Em

2017-05-15

Catecholamines modulate the impact of motivational cues on action. Such motivational biases have been proposed to reflect cue-based, 'Pavlovian' effects. Here, we assess whether motivational biases may also arise from asymmetrical instrumental learning of active and passive responses following reward and punishment outcomes. We present a novel paradigm, allowing us to disentangle the impact of reward and punishment on instrumental learning from Pavlovian response biasing. Computational analyses showed that motivational biases reflect both Pavlovian and instrumental effects: reward and punishment cues promoted generalized (in)action in a Pavlovian manner, whereas outcomes enhanced instrumental (un)learning of chosen actions. These cue- and outcome-based biases were altered independently by the catecholamine enhancer melthylphenidate. Methylphenidate's effect varied across individuals with a putative proxy of baseline dopamine synthesis capacity, working memory span. Our study uncovers two distinct mechanisms by which motivation impacts behaviour, and helps refine current models of catecholaminergic modulation of motivated action.

Anticipatory responses of catecholamines on muscle force production.

PubMed

French, Duncan N; Kraemer, William J; Volek, Jeff S; Spiering, Barry A; Judelson, Daniel A; Hoffman, Jay R; Maresh, Carl M

2007-01-01

Few data exist on the temporal relationship between catecholamines and muscle force production in vivo. The purpose of this study was to examine the influence of preexercise arousal on sympathoadrenal neurohormones on muscular force expression during resistance exercise. Ten resistance-trained men completed two experimental conditions separated by 7 days: 1) acute heavy resistance exercise protocol (AHREP; 6 x 10 repetitions parallel squats, 80% 1 repetition maximum) and 2) control (Cont; rest). Peak force (F(peak)) was recorded during a maximal isometric squat preceding each set and mean force (F(mean)) was measured during each set. Serial venous blood samples were collected before the AHREP and immediately preceding each set. Blood collection times were matched during Cont. Preexercise epinephrine (Epi), norepinephrine (NE), and dopamine (DA) increased (P or= 0.05) in muscular performance (F(peak), F(mean)) during AHREP and that five subjects (F(reducers)) had significant reductions in F(peak) and F(mean). Integrated area under the curve for Epi, NE, and F(peak) were greater (P < 0.02) for F(maintainers) than F(reducers). In conclusion, an anticipatory rise in catecholamines existed, which may be essential for optimal force production at the onset of exercise.

Very high volume hemofiltration with the Cascade system in septic shock patients.

PubMed

Quenot, Jean-Pierre; Binquet, Christine; Vinsonneau, Christophe; Barbar, Saber-David; Vinault, Sandrine; Deckert, Valerie; Lemaire, Stéphanie; Hassain, Ali Ait; Bruyère, Rémi; Souweine, Bertrand; Lagrost, Laurent; Adrie, Christophe

2015-12-01

We compared hemodynamic and biological effects of the Cascade system, which uses very high volume hemofiltration (HVHF) (120 mL kg(-1) h(-1)), with those of usual care in patients with septic shock. Multicenter, prospective, randomized, open-label trial in three intensive care units (ICU). Adults with septic shock with administration of epinephrine/norepinephrine were eligible. Patients were randomized to usual care plus HVHF (Cascade group), or usual care alone (control group). Primary end point was the number of catecholamine-free days up to 28 days after randomization. Secondary end points were number of days free of mechanical ventilation, renal replacement therapy (RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality. We included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were comparable. Median number of catecholamine-free days was 22 [IQR 11-23] vs 20 [0-25] for Cascade vs control; there was no significant difference even after adjustment. There was no significant difference in number of mechanical ventilation-free days or ICU requirement. Median number of RRT-free days was 85 [46-90] vs 74 [0-90] for Cascade vs control groups, p = 0.42. By multivariate analysis, the number of RRT-free days was significantly higher in the Cascade group (up to 25 days higher after adjustment). There was no difference in mortality at 7, 28, or 90 days. Very HVHF using the Cascade system can safely be used in patients presenting with septic shock, but it was not associated with a reduction in the need for catecholamines during the first 28 days.

Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

PubMed Central

Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

2008-01-01

Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

Neonatal overfeeding increases capacity for catecholamine biosynthesis from the adrenal gland acutely and long-term in the male rat.

PubMed

Sominsky, Luba; Ong, Lin Kooi; Ziko, Ilvana; Dickson, Phillip W; Spencer, Sarah J

2018-07-15

A poor nutritional environment during early development has long been known to increase disease susceptibility later in life. We have previously shown that rats that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal axis responses to immune stress in adulthood, particularly due to an altered capacity of the adrenal to respond to an immune challenge. Here we hypothesised that neonatal overfeeding similarly affects the sympathomedullary system, testing this by investigating the biochemical function of tyrosine hydroxylase (TH), the first rate-limiting enzyme in the catecholamine synthesis. We also examined changes in adrenal expression of the leptin receptor and in mitogen-activated protein kinase (MAPK) signalling. During the neonatal period, we saw age-dependent changes in TH activity and phosphorylation, with neonatal overfeeding stimulating increased adrenal TH specific activity at postnatal days 7 and 14, along with a compensatory reduction in total TH protein levels. This increased TH activity was maintained into adulthood where neonatally overfed rats exhibited increased adrenal responsiveness 30 min after an immune challenge with lipopolysaccharide, evident in a concomitant increase in TH protein levels and specific activity. Neonatal overfeeding significantly reduced the expression of the leptin receptor in neonatal adrenals at postnatal day 7 and in adult adrenals, but did not affect MAPK signalling. These data suggest neonatal overfeeding alters the capacity of the adrenal to synthesise catecholamines, both acutely and long term, and these effects may be independent of leptin signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan.

PubMed

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2017-03-01

Myxedema coma is a life-threatening and emergency presentation of hypothyroidism. However, the clinical features and outcomes of this condition have been poorly defined because of its rarity. We conducted a retrospective observational study of patients diagnosed with myxedema coma from July 2010 through March 2013 using a national inpatient database in Japan. We investigated characteristics, comorbidities, treatments, and in-hospital mortality of patients with myxedema coma. We identified 149 patients diagnosed with myxedema coma out of approximately 19 million inpatients in the database. The mean (standard deviation) age was 77 (12) years, and two-thirds of the patients were female. The overall proportion of in-hospital mortality among cases was 29.5%. The number of patients was highest in the winter season. Patients treated with steroids, catecholamines, or mechanical ventilation showed higher in-hospital mortality than those without. Variations in type and dosage of thyroid hormone replacement were not associated with in-hospital mortality. The most common comorbidity was cardiovascular diseases (40.3%). The estimated incidence of myxedema coma was 1.08 per million people per year in Japan. Multivariable logistic regression analysis revealed that higher age and use of catecholamines (with or without steroids) were significantly associated with higher in-hospital mortality. The present study identified the clinical characteristics and outcomes of patients with myxedema coma using a large-scale database. Myxedema coma mortality was independently associated with age and severe conditions requiring treatment with catecholamines. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Psychological stress during exercise: immunoendocrine and oxidative responses.

PubMed

Huang, Chun-Jung; Webb, Heather E; Evans, Ronald K; McCleod, Kelly A; Tangsilsat, Supatchara E; Kamimori, Gary H; Acevedo, Edmund O

2010-12-01

The purpose of this study was to examine the changes in catecholamines (epinephrine [EPI] and norepinephrine [NE]), interleukin-2 (IL-2) and a biomarker of oxidative stress (8-isoprostane) in healthy individuals who were exposed to a dual challenge (physical and psychological stress). Furthermore, this study also examined the possible relationships between catecholamines (NE and EPI) and 8-isoprostane and between IL-2 and 8-isoprostane following a combined physical and psychological challenge. Seven healthy male subjects completed two experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% VO(2max) for 37 min, while the dual-stress condition (DSC) included 20 min of a mental challenge while cycling. DSC showed greater EPI and 8-isoprostane levels (significant condition by time interaction). NE and IL-2 revealed significant change across time in both conditions. In addition, following dual stress, EPI area-under-the-curve (AUC) demonstrated a positive correlation with NE AUC and IL-2 AUC. NE AUC was positively correlated with IL-2 AUC and peak 8-isoprostane, and peak IL-2 was positively correlated with peak 8-isoprostane in response to a dual stress. The potential explanation for elevated oxidative stress during dual stress may be through the effects of the release of catecholamines and IL-2. These findings may further provide the potential explanation that dual stress alters physiological homeostasis in many occupations including firefighting, military operations and law enforcement. A greater understanding of these responses to stress can assist in finding strategies (e.g. exercise training) to overcome the inherent psychobiological challenges associated with physically and mentally demanding professions.

Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

PubMed

Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

2013-05-01

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir

NASA Astrophysics Data System (ADS)

Kvetňanský, R.; Noskov, V. B.; Blazicek, P.; Gharib, C.; Popova, I. A.; Gauquelin, G.; Macho, L.; Guell, A.; Grigoriev, A. I.

The activity of the sympathoadrenal system in cosmonauts was studied by measuring plasma and urinary catecholamines and their metabolites and conjugates. The appliance Plasma 02 was used for collecting, processing, and storing blood and urine samples from the cosmonauts during the course of a 25-day flight on board the station Mir. Plasma and urine concentrations of adrenaline (A), noradrenaline (NA), and dopamine (DA) as well as urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA), and plasma levels of catecholamine sulphates were determined before, during and after the space flight. Plasma NA levels were slightly elevated on day 9 and plasma A on day 20, whereas plasma DA levels were unchanged. However, most of the changes were within the normal range of control values. Sulphates of plasma catecholamines did not change during flight but they were significantly elevated after landing. Urinary levels of A, NA, DA, VMA, and HVA were comparable with preflight values but were elevated at the different intervals studied after landing. The results obtained suggest that in the short period of about 9 days of the cosmonaut's stay in space the sympathoadrenal system was slightly activated indicating a mild stressful influence of the initial period of flight. This short-term space flight compared to long-term flight did not as markedly activate the sympathoadrenal system during the process of re-adaptation to Earth's gravity after landing. Our data suggest that weightlessness is not a stressful factor activating the sympathoadrenal system but it sensitizes the responsiveness of this system during the re-adaptation period after space flight.

Neuropeptide y gates a stress-induced, long-lasting plasticity in the sympathetic nervous system.

PubMed

Wang, Qian; Wang, Manqi; Whim, Matthew D

2013-07-31

Acute stress evokes the fight-or-flight reflex, which via release of the catecholamine hormones affects the function of every major organ. Although the reflex is transient, it has lasting consequences that produce an exaggerated response when stress is reexperienced. How this change is encoded is not known. We investigated whether the reflex affects the adrenal component of the sympathetic nervous system, a major branch of the stress response. Mice were briefly exposed to the cold-water forced swim test (FST) which evoked an increase in circulating catecholamines. Although this hormonal response was transient, the FST led to a long-lasting increase in the catecholamine secretory capacity measured amperometrically from chromaffin cells and in the expression of tyrosine hydroxylase. A variety of approaches indicate that these changes are regulated postsynaptically by neuropeptide Y (NPY), an adrenal cotransmitter. Using immunohistochemistry, RT-PCR, and NPY(GFP) BAC mice, we find that NPY is synthesized by all chromaffin cells. Stress failed to increase secretory capacity in NPY knock-out mice. Genetic or pharmacological interference with NPY and Y1 (but not Y2 or Y5) receptor signaling attenuated the stress-induced change in tyrosine hydroxylase expression. These results indicate that, under basal conditions, adrenal signaling is tonically inhibited by NPY, but stress overrides this autocrine negative feedback loop. Because acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, these postsynaptic changes appear to be an adaptive response. We conclude that the sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity.

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy.

PubMed

Tidholm, Anna; Häggström, Jens; Hansson, Kerstin

2005-10-01

To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.

Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.

PubMed

Yogeeta, Surinder Kumar; Raghavendran, Hanumantha Rao Balaji; Gnanapragasam, Arunachalam; Subhashini, Rajakannu; Devaki, Thiruvengadam

2006-10-27

Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

Stress-induced cardiomyopathy caused by heat stroke.

PubMed

Chen, Wei-Ta; Lin, Cheng-Hsin; Hsieh, Ming-Hsiung; Huang, Chun-Yao; Yeh, Jong-Shiuan

2012-07-01

Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy. Copyright © 2011. Published by Mosby, Inc.

Neuroanatomical Evidence for Catecholamines as Modulators of Audition and Acoustic Behavior in a Vocal Teleost.

PubMed

Forlano, Paul M; Sisneros, Joseph A

2016-01-01

The plainfin midshipman fish (Porichthys notatus) is a well-studied model to understand the neural and endocrine mechanisms underlying vocal-acoustic communication across vertebrates. It is well established that steroid hormones such as estrogen drive seasonal peripheral auditory plasticity in female Porichthys in order to better encode the male's advertisement call. However, little is known of the neural substrates that underlie the motivation and coordinated behavioral response to auditory social signals. Catecholamines, which include dopamine and noradrenaline, are good candidates for this function, as they are thought to modulate the salience of and reinforce appropriate behavior to socially relevant stimuli. This chapter summarizes our recent studies which aimed to characterize catecholamine innervation in the central and peripheral auditory system of Porichthys as well as test the hypotheses that innervation of the auditory system is seasonally plastic and catecholaminergic neurons are activated in response to conspecific vocalizations. Of particular significance is the discovery of direct dopaminergic innervation of the saccule, the main hearing end organ, by neurons in the diencephalon, which also robustly innervate the cholinergic auditory efferent nucleus in the hindbrain. Seasonal changes in dopamine innervation in both these areas appear dependent on reproductive state in females and may ultimately function to modulate the sensitivity of the peripheral auditory system as an adaptation to the seasonally changing soundscape. Diencephalic dopaminergic neurons are indeed active in response to exposure to midshipman vocalizations and are in a perfect position to integrate the detection and appropriate motor response to conspecific acoustic signals for successful reproduction.

Distinguishing splanchnic nerve and chromaffin cell stimulation in mouse adrenal slices with fast-scan cyclic voltammetry

PubMed Central

Walsh, Paul L.; Petrovic, Jelena

2011-01-01

Electrical stimulation is an indispensible tool in studying electrically excitable tissues in neurobiology and neuroendocrinology. In this work, the consequences of high-intensity electrical stimulation on the release of catecholamines from adrenal gland slices were examined with fast-scan cyclic voltammetry at carbon fiber microelectrodes. A biphasic signal, consisting of a fast and slow phase, was observed when electrical stimulations typically used in tissue slices (10 Hz, 350 μA biphasic, 2.0 ms/phase pulse width) were applied to bipolar tungsten-stimulating electrodes. This signal was found to be stimulation dependent, and the slow phase of the signal was abolished when smaller (≤250 μA) and shorter (1 ms/phase) stimulations were used. The slow phase of the biphasic signal was found to be tetrodotoxin and hexamethonium independent, while the fast phase was greatly reduced using these pharmacological agents. Two different types of calcium responses were observed, where the fast phase was abolished by perfusion with a low-calcium buffer while both the fast and slow phases could be modulated when Ca2+ was completely excluded from the solution using EGTA. Perfusion with nifedipine resulted in the reduction of the slow catecholamine release to 29% of the original signal, while the fast phase was only decreased to 74% of predrug values. From these results, it was determined that high-intensity stimulations of the adrenal medulla result in depolarizing not only the splanchnic nerves, but also the chromaffin cells themselves resulting in a biphasic catecholamine release. PMID:21048165

Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

PubMed

Park, Min Jung; Guest, Christopher B; Barnes, Meredith B; Martin, Jonathan; Ahmad, Uzma; York, Jason M; Freund, Gregory G

2008-11-01

Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal. Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines. Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal. These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.

DBH deficiency in an elderly patient: efficacy and safety of chronic droxidopa.

PubMed

Despas, Fabien; Pathak, A; Berry, M; Cagnac, R; Massabuau, P; Liozon, E; Galinier, M; Senard, J M

2010-06-01

We describe the effects of chronic droxidopa in a patient with Dopamine beta-hydroxylase deficiency diagnosed at the age of 73. Investigations were performed to assess sympathetic activity (MIBG scintigraphy, catecholamines) and cardiovascular droxidopa safety.

Automated differential fluorometric analysis of norepinephrine and epinephrine in blood plasma and urine.

DOT National Transportation Integrated Search

1971-04-01

An automated fluorometric trihydroxyindole procedure is described for the measurement of norepinephrine (NE) and epinephrine (E) in blood plasma or urine. The method employs conventional techniques for isolation of the catecholamines by alumina colum...

Bovine temperament impacts immunity, metabolism, and reproduction: A review

USDA-ARS?s Scientific Manuscript database

Temperament, or excitability, is a behavioral trait that has been shown to impact physiology and performance. Temperament in cattle alters the function of the hypothalamic-pituitary-adrenal axis, thereby influencing circulating concentrations of catecholamines and glucocorticoids. The physiological ...

Dynamical Systems in Neuropharmacology

DTIC Science & Technology

1992-04-15

induced hyperactivity with the selective serotonin uptake blockers fluoxetine , sertraline, or zimelidine or with the serotonin synthesis inhibitor PCPA. By...Conversely, the catecholamine synthesis inhibitor AMPT, which blocks the effects of amphetamine, did not affect the response to MDMA. We applied our scaling

High-performance Liquid Chromatography Measured Metabolites of Endogenous Catecholamines and Their Relations to Chronic Kidney Disease and High Blood Pressure in Heart Transplant Recipients.

PubMed

Wasilewski, G; Przybylowski, P; Wilusz, M; Sztefko, K; Janik, Ł; Koc-Żórawska, E; Malyszko, J

2016-06-01

Patients after solid organ transplantation, especially heart and kidneys, are prone to be hypertensive. Recently chronic kidney disease and renalase metabolism of endogenous catecholamines are thought to make major contribution to the pathogenesis of hypertension. We analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years (range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74). Diagnosis of hypertension was made on the basis of ambulatory blood pressure monitoring. Complete blood count, urea, creatinine, estimated glomerular filtration rate (eGFR), renalase in serum, and levels of metanefrine, normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with a high-performance liquid chromatography were recorded. Urine endogenous catecholamine metabolites were estimated according to creatinine clearance. Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P < .01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r = 0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r = -0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight (r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3-Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r = 0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01). Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05). Chronic kidney disease and concomitant hypertension are the most prevalent comorbidities in the population of heart transplant recipients. Urine catecholamine metabolites were related to kidney function but not to blood pressure level in the studied population. Copyright © 2016 Elsevier Inc. All rights reserved.

[The effects of perioperative continuous administration of mivazerol on early postoperative hemodynamics and plasma catecholamines after major surgery].

PubMed

Apitzsch, H; Olthoff, D; Thieme, V; Vetter, B; Wiegel, M

2000-08-01

During and after surgical procedures a strong activation of the sympatho-adrenergic system is common with correlation to adverse cardiac outcome. Several drugs (alpha 2-adrenoceptor-agonists, beta blockers) are discussed to prevent this reaction. The new alpha 2-adrenoceptor-agonist mivazerol with marked specificity for alpha 2-adrenergic receptors may be suitable for this indication. The aim of the present study was to investigate the effects of perioperative continuous administration of mivazerol on plasma catecholamines, body temperature and calculated haemodynamic parameters in the early postoperative period in cardiac risk patients undergoing non-cardiac surgery. 36 patients with known coronary heart disease or risk factors for coronary heart disease scheduled for elective abdominal or vascular surgery were included in the study. Patients received either mivazerol (n = 18) or placebo (n = 18) [initial dose 4 micrograms kg-1 for 10 minutes before induction of anaesthesia, followed by a continuous infusion of 1.5 micrograms kg-1 h-1 intraoperatively and for as long as 72 h after surgery] in a double-blinded, randomized manner. Blood pressure, heart rate and body temperature were measured every 10 minutes until 240 minutes after arrival at the ICU. During 240 minutes after arrival at the ICU measured parameters (CVP, PAP, PCWP, SaO2, SvO2, CO), calculated parameters (CI, SVR, PVR, VO2) and plasma catecholamines were measured at defined time intervalls. The plasma concentrations of epinephrine and norepinephrine and the heart rate were significantly lower in the mivazerol group in the study period. Regarding blood pressure and body temperature there were no differences between the groups. At some measuring points preload was higher in the mivazerol group, but there were no differences between the groups for measured (SaO2, SvO2, CO) and calculated (CI, SVR, PVR, VO2) cardiorespiratory parameters. The incidence of shivering, nausea and vomiting were similar in both groups. Continuous, perioperative administration of mivazerol decreased the heart rate and the plasma catecholamines in the early postoperative period, but did not affect blood pressure, body temperature and the incidence of shivering. There were also no effects of mivazerol on calculated haemodynamic parameters (CO, SVR, PVR, VO2). These findings show a selective decrease in heart rate by Mivazerol without markedly cardiorespiratory side effects.

Ryanodine Receptor Calcium Leak in Circulating B-Lymphocytes as a Biomarker in Heart Failure.

PubMed

Kushnir, Alexander; Santulli, Gaetano; Reiken, Steven R; Coromilas, Ellie; Godfrey, Sarah J; Brunjes, Danielle L; Colombo, Paolo C; Yuzefpolskaya, Melana; Sokol, Seth I; Kitsis, Richard N; Marks, Andrew R

2018-03-28

Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2 + is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2 + release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2 + leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2 + release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2 + leak, contributing to myopathy and weakness. Circulating B-lymphocytes express RyR1 and catecholamine responsive signaling cascades, making them a potential surrogate for defects in intracellular Ca2 + handling due to leaky RyR channels in CHF. Methods -Whole blood was collected from patients with CHF, CHF status-post left-ventricular assist devices (LVAD), and controls. Blood was also collected from mice with ischemic CHF, ischemic CHF + S107 (a drug that specifically reduces RyR channel Ca2 + leak), and WT controls. Channel macromolecular complex was assessed by immunostaining RyR1 immunoprecipitated from lymphocyte enriched preparations. RyR1 Ca2 + leak was assessed using flow cytometry to measure Ca2 + fluorescence in B-lymphocytes, in the absence and presence of RyR1 agonists that empty RyR1 Ca2 + stores within the endoplasmic reticulum (ER). Results -Circulating B-lymphocytes from humans and mice with CHF exhibited remodeled RyR1 and decreased ER Ca2 + stores, consistent with chronic intracellular Ca2 + leak. This Ca2 + leak correlated with circulating catecholamine levels. The intracellular Ca2 + leak was significantly reduced in mice treated with the Rycal S107. CHF patients treated with LVAD exhibited a heterogeneous response. Conclusions -In CHF, B-lymphocytes exhibit remodeled leaky RyR1 channels and decreased ER Ca2 + stores consistent with chronic intracellular Ca2 + leak. RyR1 mediated Ca2 + leak in B-lymphocytes assessed using flow cytometry provides a surrogate measure of intracellular Ca2 + handling and systemic sympathetic burden, presenting a novel biomarker for monitoring response to pharmacologic and mechanical CHF therapy.

Effects of perch access on physiological parameters in caged White Leghorn pullets

USDA-ARS?s Scientific Manuscript database

The neuroendocrine system controls animals' adaptability to their environments by releasing psychotropic compounds such as catecholamines [epinephrine (EP), norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5-HT). Changes of these neuroendocrine compounds have been used ...

Perilipin overexpression in mice protects against diet-induced obesity

USDA-ARS?s Scientific Manuscript database

Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand t...

Exercise: Applications to Childhood ADHD

ERIC Educational Resources Information Center

Wigal, Sharon B.; Emmerson, Natasha; Gehricke, Jean-G.; Galassetti, Pietro

2013-01-01

ADHD is the most common neurobehavioral disorder of childhood, presenting with pervasive and impairing symptoms of inattention, hyperactivity, impulsivity, or a combination. The leading hypothesis of the underlying physiology of this disorder of inattention and/or hyperactivity-impulsivity is based on catecholamine dysfunction. Pharmacotherapy…

Marine Bivalve Cellular Responses to Beta Blocker Exposures

EPA Science Inventory

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated whi...

Pharmacology Experiments on the Computer.

ERIC Educational Resources Information Center

Keller, Daniel

1990-01-01

A computer program that replaces a set of pharmacology and physiology laboratory experiments on live animals or isolated organs is described and illustrated. Five experiments are simulated: dose-effect relationships on smooth muscle, blood pressure and catecholamines, neuromuscular signal transmission, acetylcholine and the circulation, and…

Presence and function of dopamine transporter (DAT) in stallion sperm: dopamine modulates sperm motility and acrosomal integrity.

PubMed

Urra, Javier A; Villaroel-Espíndola, Franz; Covarrubias, Alejandra A; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I

2014-01-01

Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP(+)), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.

Presence and Function of Dopamine Transporter (DAT) in Stallion Sperm: Dopamine Modulates Sperm Motility and Acrosomal Integrity

PubMed Central

Covarrubias, Alejandra A.; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I.

2014-01-01

Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP+), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility. PMID:25402186

New semi-quantitative 123I-MIBG estimation method compared with scoring system in follow-up of advanced neuroblastoma: utility of total MIBG retention ratio versus scoring method.

PubMed

Sano, Yuko; Okuyama, Chio; Iehara, Tomoko; Matsushima, Shigenori; Yamada, Kei; Hosoi, Hajime; Nishimura, Tsunehiko

2012-07-01

The purpose of this study is to evaluate a new semi-quantitative estimation method using (123)I-MIBG retention ratio to assess response to chemotherapy for advanced neuroblastoma. Thirteen children with advanced neuroblastoma (International Neuroblastoma Risk Group Staging System: stage M) were examined for a total of 51 studies with (123)I-MIBG scintigraphy (before and during chemotherapy). We proposed a new semi-quantitative method using MIBG retention ratio (count obtained with delayed image/count obtained with early image with decay correction) to estimate MIBG accumulation. We analyzed total (123)I-MIBG retention ratio (TMRR: total body count obtained with delayed image/total body count obtained with early image with decay correction) and compared with a scoring method in terms of correlation with tumor markers. TMRR showed significantly higher correlations with urinary catecholamine metabolites before chemotherapy (VMA: r(2) = 0.45, P < 0.05, HVA: r(2) = 0.627, P < 0.01) than MIBG score (VMA: r(2) = 0.19, P = 0.082, HVA: r(2) = 0.25, P = 0.137). There were relatively good correlations between serial change of TMRR and those of urinary catecholamine metabolites (VMA: r(2) = 0.274, P < 0.001, HVA: r(2) = 0.448, P < 0.0001) compared with serial change of MIBG score and those of tumor markers (VMA: r(2) = 0.01, P = 0.537, HVA: 0.084, P = 0.697) during chemotherapy for advanced neuroblastoma. TMRR could be a useful semi-quantitative method for estimating early response to chemotherapy of advanced neuroblastoma because of its high correlation with urine catecholamine metabolites.

Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

PubMed

Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeon-Joong; Hwang, Sung-Hee; Lee, Myung Koo; Bae, Chun-Sik; Kim, Hyoung-Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

2016-01-26

Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site.

PubMed

Roberts, Kenneth M; Khan, Crystal A; Hinck, Cynthia S; Fitzpatrick, Paul F

2014-12-16

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The k(cat)/K(phe) value is down 10⁴ for the mutant enzyme, and the K(m) value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain.

Norepinephrine and thyroxine are predictors of fat mass gain in humans with cold-induced brown adipose tissue activation.

PubMed

Begaye, Brittany; Piaggi, Paolo; Thearle, Marie S; Haskie, Kaitlyn; Walter, Mary; Schlögl, Mathias; Bonfiglio, Susan; Krakoff, Jonathan; Vinales, Karyne L

2018-05-16

In healthy adults with detectable cold-induced brown fat activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Twelve healthy volunteers (7M/5F) with positive CIBA (>2 standardized uptake value (g/mL)) had 24-h energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron-emission tomography/computed tomography scans were performed after exposure to 16°C for 2h to quantify CIBA. CIBA, 24hEE during EBL and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 (fT3) and free t4 (fT4). Body composition at baseline and six months by DXA. Lower urinary norepinephrine and fT4 were associated with higher CIBA (r = ‒0.65, p = 0.03 and r = ‒0.75, p<0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (p=0.77). Lower CIBA (β = ̶̶ 3.5 kg/SUV, p<0.01) predicted fat mass gain; whereas, higher urinary norepinephrine and fT4 predicted future fat mass gain at 6 months (β = 3.0 kg per two-fold difference in norepinephrine, p=0.03; β = 1.2 kg per 0.1 ng/dL difference in fT4, p=0.03, respectively). Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

[Premature immunosenescence in catecholamines syntesis deficient mice. Effect of social environment].

PubMed

Garrido, Antonio; Cruces, Julia; Iriarte, Idoia; Hernández-Sánchez, Catalina; de Pablo, Flora; de la Fuente, Mónica

Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. To determine if an haploinsufficiency of tyrosine hydroxylase (TH), the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Adult (9±1 months) male ICR-CD1 mice with deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT>50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT<50%, TH-HZ<50% and TH-HZ>50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. TH-HZ>50% mice showed a deteriorated function and redox state in leukocytes respect to WT>50% and similar to old mice. However, TH-HZ<50% animals had similar values to those found in WT<50% mice. The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions

PubMed Central

DeWitt, Elizabeth S.; Black, Katherine J.; Thiagarajan, Ravi R.; DiNardo, James A.; Colan, Steven D.; McGowan, Francis X.

2016-01-01

Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P < 0.001). The use of triiodothyronine and milrinone was not associated with significant changes in cardiac output, contractility or diastolic function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r2 = 0.72), dP/dtmin (r2 = 0.70), and stroke work (r2 = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility. PMID:27150829

Physical exercise introduced after weaning enhances pancreatic islet responsiveness to glucose and potentiating agents in adult MSG-obese rats.

PubMed

Ribeiro, R A; Bonfleur, M L; Vanzela, E C; Zotti, A I; Scomparin, D X; Boschero, A C; Balbo, S L

2014-08-01

Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8-8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1-16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K(+) stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 μmol/l), forskolin (10 μmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells.

PubMed

Lenis, Yasser Y; Wang, Xiaoqiu; Tang, Wanjin; Wu, Guoyao; Bazer, Fuller W

2016-10-01

Embryonic survival requires histotrophic nutrition, including molecules secreted or transported into the uterine lumen by uterine epithelia. L-Arginine (Arg) is a common substrate for synthesis of nitric oxide, ornithine, proline, glutamate, creatinine, urea, polyamines and agmatine. Agmatine (Agm) is a product of arginine decarboxylation and it is a substrate for agmatinase for synthesis of putrescine and other polyamines in the ovine conceptus. Polyamines are essential for conceptus development. Therefore, this study compared effects of Arg and Agm on the behavior of ovine trophectoderm (oTr1) cells cultured in vitro. Arg, but not Agm, increased proliferation and migration of oTr1 cells, but neither Arg nor Agm affected cell adhesion. The total amount of IFNT in culture medium of oTr1 cells was increased by Arg, but Agm increased the IFNT production per oTr1 cell. Arg and Agm plus Arg decreased secretion of dopamine and norepinephrine by oTr1 cells. Agm upregulates expression of mRNAs SLC7A1, agmatinase and OAZ2 while the combination of Arg and Agm decreased expression of mRNAs for ODC1, SLC7A1, OAZ1 and OAZ3 by oTr1 cells. Although Agm does not stimulate proliferation, migration or adhesion of oTr1 cells or their secretion of catecholamines, Agm did increase transcription of SLC7A1, agmatinase and OAZ2 genes which would increase the capacity of oTr1 cells to produce polyamines. Collectively, our findings suggest a role for Arg and Agm in the regulation of transport of basic amino acids (including Arg), polyamine synthesis, and secretion of catecholamines by oTr1 cells.

Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

PubMed

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

Effects of Pre-Experience of Social Exclusion on Hypothalamus-Pituitary-Adrenal Axis and Catecholaminergic Responsiveness to Public Speaking Stress

PubMed Central

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Backround Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Methods Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Results Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. Conclusions We replicated our previous study result of a supressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective. PMID:23573255

Activation of Phenylalanine Hydroxylase by Phenylalanine Does Not Require Binding in the Active Site

PubMed Central

2015-01-01

Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein’s regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The kcat/Kphe value is down 104 for the mutant enzyme, and the Km value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain. PMID:25453233

Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

PubMed Central

Vargas-Alarcón, Gilberto; Fragoso, José-Manuel; Cruz-Robles, David; Vargas, Angélica; Vargas, Alfonso; Lao-Villadóniga, José-Ignacio; García-Fructuoso, Ferrán; Ramos-Kuri, Manuel; Hernández, Fernando; Springall, Rashidi; Bojalil, Rafael; Vallejo, Maite; Martínez-Lavín, Manuel

2007-01-01

Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results. PMID:17961261

Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia.

PubMed

Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

2015-02-01

Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Role of P-glycoprotein and permeability upon the brain distribution and pharmacodynamics of etamicastat: a comparison with nepicastat.

PubMed

Loureiro, Ana I; Bonifácio, Maria João; Fernandes-Lopes, Carlos; Pires, Nuno; Igreja, Bruno; Wright, Lyndon C; Soares-da-Silva, Patrício

2015-01-01

1. This study explores the impact of permeability and P-glycoprotein (P-gp) efflux, upon brain exposure to etamicastat, a new dopamine-β-hydroxylase (DBH) inhibitor and consequently brain levels of catecholamines. 2. Brain exposure to etamicastat (10 mg/kg), following intravenous administration to mice, was residual and upon oral administration of the same dose no compound was detected, concurring with the absence of effects upon brain catecholamines. The intravenous co-administration of elacridar (1.0 mg/kg), a known P-gp/BCRP dual modulator, significantly increased brain etamicastat exposure, but the levels attained were very low when compared to those of nepicastat, a centrally active DBH inhibitor. 3. In vitro permeability studies from apical-to-basal direction conducted in Caco-2 cells and MDCK-II cells showed that etamicastat apparent permeability was 1.2 × 10(-5) and 1.1 × 10(-6 )cm/s, respectively, 5- and 50-fold lower as compared to nepicastat. The secretory efflux ratio in MDCK-II cells overexpressing human P-gp showed an efflux ratio greater than 2, for both compounds, which was significantly decreased by elacridar. Despite its lower bioavailability and higher clearance, as compared to nepicastat, etamicastat showed preferential distribution to peripheral tissues and high plasma free fraction (15.5%), which may explain its effects upon peripheral DBH and catecholamine levels. 4. Though P-gp-mediated efflux may contribute to the limited brain penetration of etamicastat, the low permeability along with the pharmacokinetic properties of etamicastat may be perceived as the main contributors for its peripheral selectivity, which is advantageous for a cardiovascular drug candidate.

[The influence of single moderate exercise on the sympathetic nervous system activity in patients with essential hypertension].

PubMed

Gajek, Jacek; Zyśko, Dorota

2002-12-01

Sympathetic nervous system may play an important role in development and maintenance of hypertension. Its activity can be assessed by plasma levels of catecholamines, neuropeptide Y (NPY) and adrenergic receptor density. Hypertensive subjects may be more prone to reveal overactivity of sympathetic nervous system, for instance as a result of physical stress. The aim of the study was to determine the activity of sympathetic nervous system in young patients with newly recognized, untreated mild hypertension. The study was carried out in 22 patients (age 38.5 +/- 10.3 years) and 20 normotensive volunteers (age 38.5 +/- 8.6 years) as a control group, matched for sex. Density of alpha 2- and beta-adrenergic receptors using 3H-yohimbine and 125I-cyanopindolol respectively, total catecholamines and plasma renin activity using radioenzymatic assay, neuropeptide Y and aldosterone using radioimmunoassay were assessed in the blood taken in the supine position and after moderate bicycle ergometer exercise. Plasma concentration of NPY at rest did not differ between the groups, but increased significantly after exercise and was greater in hypertensive patients (p < 0.05). The density of alpha 2- and beta-adrenergic receptors at rest and after exercise in hypertensive subjects was unchanged when comparing to healthy individuals. The plasma concentrations of endogenous catecholamines, plasma renin activity and aldosterone level increase during exercise in both studied groups (p < 0.05). Aldosterone level was higher in hypertensive patients at rest (p < 0.05). There was a negative correlation between baseline aldosterone and NPY levels in hypertensive patients (r = -0.44, p < 0.05). Moderate exercise in hypertensive subjects causes the hyperactivity of sympathetic nervous system expressed as increase of NPY plasma level.

The role of chromogranin A in the management of patients with phaeochromocytoma.

PubMed

Grossrubatscher, Erika; Dalino, Paolo; Vignati, Federico; Gambacorta, Marcello; Pugliese, Raffaele; Boniardi, Marco; Rossetti, Ornella; Marocchi, Alessandro; Bertuzzi, Michaela; Loli, Paola

2006-09-01

Chromogranin A (CgA) is the most accurate general marker of neuroendocrine tumours. Supranormal CgA concentrations have been recorded in patients with tumours of neuroectodermal origin such as phaeochromocytoma and paraganglioma. The present study was performed to assess the role of CgA determination in the management of patients with phaeochromocytoma, in comparison with urinary catecholamines and their metabolites. The patients studied included 22 cases with phaeochromocytoma at initial presentation or at relapse some years after surgical cure or during follow-up of a malignant phaeochromocytoma. Seventeen patients were evaluated before and after surgical removal of phaeochromocytoma. To assess the specificity of the hormonal parameters, 20 subjects were enrolled as controls; they were from a group of patients referred to our observation for possible phaeochromocytoma and who were subsequently proven not to have the disease. Urinary epinephrine and norepinephrine were supranormal in 82% and 77% of patients, respectively. Urinary metanephrines and normetanephrines were supranormal in 84% and 89% of patients, respectively. The combination of urinary metanephrine and normetanephrine had a sensitivity of 100% in identifying a phaeochromocytoma. CgA was supranormal in 91% of patients. Combining the results of CgA and urinary catecholamines (epinephrine and norepinephrine), the sensitivity for diagnosis of phaeochromocytoma was 100%. Urinary catecholamines, metabolites (metanephrine and normetanephrine) and CgA levels in patients with malignant phaeochromocytoma did not differ significantly from those of patients with benign lesions. In most cases, CgA normalized after surgery. Our results indicate that CgA is a good marker of phaeochromocytoma; measurement of CgA could have a role in the follow-up of patients operated on for phaeochromocytoma.

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

PubMed

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

PubMed

Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

2016-01-01

Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Posttranscriptional regulation of adrenal TH gene expression contributes to the maladaptive responses triggered by insulin-induced recurrent hypoglycemia

PubMed Central

Kudrick, Necla; Chan, Owen; La Gamma, Edmund F; Kim, Juhye Lena; Tank, Arnold William; Sterling, Carol; Nankova, Bistra B

2015-01-01

Acute metabolic stress such as insulin-induced hypoglycemia triggers a counterregulatory response during which the release of catecholamines (epinephrine), the activation of tyrosine hydroxylase (TH) enzyme and subsequent compensatory catecholamine biosynthesis occur in the adrenal medulla. However, recurrent exposure to hypoglycemia (RH), a consequence of tight glycemic control in individuals with type 1 and type 2 diabetes compromises this physiological response. The molecular mechanisms underlying the maladaptive response to repeated glucose deprivation are incompletely understood. We hypothesize that impaired epinephrine release following RH reflects altered regulation of adrenal catecholamine biosynthesis. To test this hypothesis, we compared the effect of single daily (RH) and twice-daily episodes of insulin-induced hypoglycemia (2RH) on adrenal epinephrine release and production in normal rats. Control animals received saline injections under similar conditions (RS and 2RS, respectively). Following 3 days of treatment, we assessed the counterregulatory hormonal responses during a hypoglycemic clamp. Changes in adrenal TH gene expression were also analyzed. The counterregulatory responses, relative TH transcription and TH mRNA levels and Ser40-TH phosphorylation (marker for enzyme activation) were induced to a similar extent in RS, 2RS, and RH groups. In contrast, epinephrine and glucagon responses were attenuated in the 2RH group and this was associated with a limited elevation of adrenal TH mRNA, rapid inactivation of TH enzyme and no significant changes in TH protein. Our results suggest that novel posttranscriptional mechanisms controlling TH mRNA and activated TH enzyme turnover contribute to the impaired epinephrine responses and may provide new therapeutic targets to prevent HAAF. PMID:25713330

Influences of graded dose of melatonin on the levels of blood glucose and adrenal catecholamines in male roseringed parakeets (Psittacula krameri ) under different photoperiods.

PubMed

Maitra, S K; Dey, M; Dutta, S; Bhattacharya, S; Dey, R; Sengupta, A

2000-12-01

Effects of daily evening (just before the onset of darkness in a 24 h light dark cycle) administration of graded doses (25, 50, or 100 microg/100 g body wt./day for 30 days) of melatonin on the concentrations of blood glucose and adrenal catecholamines were studied in sexually active male roseringed parakeets under natural (NP; approximately 12L: 12D) and artificial long (LP; 16L: 8D) and short (SP; 8L: 16D) photoperiods. Blood samples and adrenal glands were collected from each bird during the mid-day on the following day of the last treatment. The concentrations of glucose in blood and epinephrine (E) and norepinephrine (NE) in the adrenals were measured. The results of the study indicated that exogenous melatonin induces hypo- or hyperglycemia depending on the dose of hormone administered as well as to the length of photoperiod to which birds were exposed. The levels of E and NE in the adrenals were shown also to vary in relation to photoperiod and the dose of melatonin administered. But the nature of the influence of melatonin becomes different under altered photoperiodic conditions. It appears that short photoperiods are more effective than long photoperiods as a modulator of glycemic and adrenal catecholaminergic responses to exogenous melatonin. A statistically significant correlation between the levels of blood glucose and that of E and NE in the adrenals was found in the control birds, but not in the melatonin treated birds. The results suggested that the responses of blood glucose and adrenal catecholamines to the treatment with melatonin in the roseringed parakeets may not be dependent on each other.

Behavioral and Physiological Effects of Psychological Stress in Rats.

DTIC Science & Technology

1982-11-01

and to an increase in acetyl- choline levels (1, 3, 38). Pharmacological treatments that deplete central catecholamines mimic the behavioral effects...testing, each animal was sacrificed (Halo- * thane overdose ). The stomach was removed, opened, and examined for ulcers, which were specified by the

Exploring Non-Thermal Radiofrequency Bioeffects for Novel Military Applications

DTIC Science & Technology

2006-11-30

catecholamine release, using cultured adrenal chromaffin cells as an i,i vitro model system, and on skeletal muscle contraction , using intact skeletal...characterization and construction of a waveguide-based exposure system for monitoring skeletal muscle contraction during exposure to 0.75-1 GHz RF

Haemodialysis, nutritional disorders and hypoglycaemia in critical care.

PubMed

Crespo, Jeiel Carlos Lamonica; Gomes, Vanessa Rossato; Barbosa, Ricardo Luís; Padilha, Katia Grillo; Secoli, Silvia Regina

2017-03-09

This study aimed to determine hypoglycemia incidence and associated factors in critically ill patients. It looked at a retrospective cohort with 106 critically ill adult patients with 48 hours of glycaemic control and 72 hours of follow up. The dependent variable, hypoglycaemia (≤70 mg/dl), was assessed with respect to independent variables: age, diet, insulin, catecholamines, haemodialysis, nursing workload and the Simplified Acute Physiology Score. Statistical analysis was performed using Student's t-test, Fisher's exact test and logistic regression at 5% significance level. Incidence of hypoglycaemia was 14.2%. Hypoglycaemia was higher in the group of patients on catecholamines (p=0.040), with higher glycaemic variability (p<0.001) and death in the intensive care unit (p=0.008). Risk factors were identified as absence of oral diet (OR 5.11; 95% CI 1.04-25.10) and haemodialysis (OR 4.28; 95% CI 1.16-15.76). Patients on haemodialysis and with no oral diet should have their glycaemic control intensified in order to prevent and/or manage hypoglycaemic episodes.

Cation interdependency in acute stressor states.

PubMed

Khan, M Usman; Komolafe, Babatunde O; Weber, Karl T

2013-05-01

Acute stressor states are inextricably linked to neurohormonal activation which includes the adrenergic nervous system. Consequent elevations in circulating epinephrine and norepinephrine unmask an interdependency that exists between K+, Mg2+ and Ca2+. Catecholamines, for example, regulate the large number of Mg2+-dependent Na/K ATPase pumps present in skeletal muscle. A hyperadrenergic state accounts for a sudden translocation of K+ into muscle and rapid appearance of hypokalemia. In the myocardium, catecholamines promote Mg2+ efflux from cardiomyocytes, whereas intracellular Ca2+ influx and overloading account for the induction of oxidative stress and necrosis of these cells with leakage of their contents, including troponins. Accordingly, acute stressor states can be accompanied by nonischemic elevations in serum troponins, together with the concordant appearance of hypokalemia, hypomagnesemia and ionized hypocalcemia, causing a delay in myocardial repolarization and electrocardiographic QTc prolongation raising the propensity for arrhythmias, including atrial fibrillation and polymorphic ventricular tachycardia. In this review, we focus on the interdependency between K+, Mg2+ and Ca2+ which are clinically relevant to acute stressor states.

Quinone Reductase 2 Is a Catechol Quinone Reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Yue; Buryanovskyy, Leonid; Zhang, Zhongtao

2008-09-05

The functions of quinone reductase 2 have eluded researchers for decades even though a genetic polymorphism is associated with various neurological disorders. Employing enzymatic studies using adrenochrome as a substrate, we show that quinone reductase 2 is specific for the reduction of adrenochrome, whereas quinone reductase 1 shows no activity. We also solved the crystal structure of quinone reductase 2 in complexes with dopamine and adrenochrome, two compounds that are structurally related to catecholamine quinones. Detailed structural analyses delineate the mechanism of quinone reductase 2 specificity toward catechol quinones in comparison with quinone reductase 1; a side-chain rotational difference betweenmore » quinone reductase 1 and quinone reductase 2 of a single residue, phenylalanine 106, determines the specificity of enzymatic activities. These results infer functional differences between two homologous enzymes and indicate that quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease.« less

Three-dimensional entertainment as a novel cause of takotsubo cardiomyopathy.

PubMed

Taylor, Montoya; Amin, Anish; Bush, Charles

2011-11-01

Takotsubo cardiomyopathy (TC) is an uncommon entity. It is known to occur in the setting of extreme catecholamine release and results in left ventricular dysfunction without evidence of angiographically definable coronary artery disease. There have been no published reports of TC occurring with visual stimuli, specifically 3-dimensional (3D) entertainment. We present a 55-year-old woman who presented to her primary care physician's office with extreme palpitations, nausea, vomiting, and malaise <48 hours after watching a 3D action movie at her local theater. Her electrocardiogram demonstrated ST elevations in aVL and V1, prolonged QTc interval, and T-wave inversions in leads I, II, aVL, and V2-V6. Coronary angiography revealed angiographically normal vessels, elevated left ventricular filling pressures, and decreased ejection fraction with a pattern of apical ballooning. The presumed final diagnosis was TC, likely due to visual-auditory-triggered catecholamine release causing impaired coronary microcirculation. © 2011 Wiley Periodicals, Inc.

Concurrent bilateral pheochromocytoma and thoracic paraganglioma during pregnancy.

PubMed

Snabboon, Thiti; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Plengvidhya, Nattachet; Sereepapong, Wisan; Sunthornyothin, Sarat; Shotelersuk, Vorasuk

2010-04-01

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.

Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.

PubMed

Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J M; Yeo, Robin; Zhang, Yue; Huynh, Frank K; Ilkayeva, Olga R; Hirschey, Matthew D; Grant, Ana R; Mair, William B

2015-02-26

Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal

PubMed Central

Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J.M.; Yeo, Robin; Zhang, Yue; Huynh, Frank K.; Ilkayeva, Olga R.; Hirschey, Matthew D.; Grant, Ana R.; Mair, William B.

2015-01-01

SUMMARY Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell-nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. PMID:25723162

Stress-related hormones in horses before and after stunning by captive bolt gun.

PubMed

Micera, Elisabetta; Albrizio, Maria; Surdo, Nicoletta C; Moramarco, Angela M; Zarrilli, Antonia

2010-04-01

In this work the slaughter-linked plasma modifications of some stress-related hormones in horses subject to standardized butchering procedures were investigated in order to highlight the compromised animal welfare during pre-slaughter handling. During pre-slaughter, animals show strong hardship behavioural patterns, probably due to being under life-threatening conditions. Blood samples from 12 male horses, ageing from 3 to 5 years, were collected before slaughtering in lairage, and during exsanguination after stunning. Catecholamines, cortisol and beta-endorphin concentrations were assessed in plasma samples by EIA. Results show that plasma beta-endorphin concentration did not increase significantly after stunning, while cortisol (P<0.05) and catecholamines (P<0.001) increased significantly. The ratio between the plasma level of norepinephrine and epinephrine decreased significantly (P<0.001) during the time considered for observation underlining a greater involvement of adrenal medulla in the stress response. Moreover these results suggest that, under stress, the release of beta-endorphin could be different from that of ACTH. 2009 Elsevier Ltd. All rights reserved.

Catecholaminergic challenge uncovers distinct Pavlovian and instrumental mechanisms of motivated (in)action

PubMed Central

Swart, Jennifer C; Froböse, Monja I; Cook, Jennifer L; Geurts, Dirk EM; Frank, Michael J; Cools, Roshan; den Ouden, Hanneke EM

2017-01-01

Catecholamines modulate the impact of motivational cues on action. Such motivational biases have been proposed to reflect cue-based, ‘Pavlovian’ effects. Here, we assess whether motivational biases may also arise from asymmetrical instrumental learning of active and passive responses following reward and punishment outcomes. We present a novel paradigm, allowing us to disentangle the impact of reward and punishment on instrumental learning from Pavlovian response biasing. Computational analyses showed that motivational biases reflect both Pavlovian and instrumental effects: reward and punishment cues promoted generalized (in)action in a Pavlovian manner, whereas outcomes enhanced instrumental (un)learning of chosen actions. These cue- and outcome-based biases were altered independently by the catecholamine enhancer melthylphenidate. Methylphenidate’s effect varied across individuals with a putative proxy of baseline dopamine synthesis capacity, working memory span. Our study uncovers two distinct mechanisms by which motivation impacts behaviour, and helps refine current models of catecholaminergic modulation of motivated action. DOI: http://dx.doi.org/10.7554/eLife.22169.001 PMID:28504638

Early life permethrin exposure leads to hypervitaminosis D, nitric oxide and catecholamines impairment.

PubMed

Fedeli, Donatella; Carloni, Manuel; Nasuti, Cinzia; Gambini, Anna; Scocco, Vitangelo; Gabbianelli, Rosita

2013-09-01

The aim of this study is to gain more knowledge on the impact of early life pesticide exposure on premature aging. The effect of a low dose of the insecticide permethrin administered to rats during early life (1/50 LD50, from 6th to 21st day of life) was analyzed by measuring some metabolites in plasma and urine of 500-day-old animals. Significant differences in early life treated rats compared to the control group were found in the plasma levels of Ca(++), Na(+), 25-hydroxy-vitamin D, adrenaline, noradrenaline, nitric oxide, cholesterol and urea while in urine only Na(+) content was different. These results add information on the impact of permethrin during the neonatal period, supporting the evidence that early life environmental exposure to xenobiotics has long-term effects, inducing modifications in adulthood that can be revealed by the analysis of some macroelements, metabolites and catecholamines in plasma, when rats are 500 days old. Copyright © 2013 Elsevier Inc. All rights reserved.

Developmental programming of O2 sensing by neonatal intermittent hypoxia via epigenetic mechanisms

PubMed Central

Nanduri, Jayasri; Prabhakar, Nanduri R.

2014-01-01

Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Carotid body chemo-reflex and catecholamine secretion from adrenal medullary chromaffin cells (AMC) are important for maintenance of cardio-respiratory homeostasis during hypoxia. This article highlights studies on the effects of IH on O2 sensing by the carotid body and AMC in neonatal rodents. Neonatal IH augments hypoxia-evoked carotid body sensory excitation and catecholamine secretion from AMC which are mediated by reactive oxygen species (ROS)-dependent recruitment of endothelin-1 and Ca2+ signaling, respectively. The effects of neonatal IH persist into adulthood. Evidence is emerging that neonatal IH initiates epigenetic mechanisms involving DNA hypermethylation contributing to long-lasting increase in ROS levels. Since adult human subjects born preterm exhibit higher incidence of sleep-disordered breathing and hypertension, DNA hypomethylating agents might offer a novel therapeutic intervention to decrease long-term cardio-respiratory morbidity caused by neonatal IH. PMID:22846496

Catecholamine excretion rates in relation to life-styles in the male population of Otmoor, Oxfordshire.

PubMed

Reynolds, V; Jenner, D A; Palmer, C D; Harrison, G A

1981-01-01

The paper gives the results of the number of analyses of aspects of life-style and dietary patterns of members of the Otmoor population, in relation to their catecholamine excretion rates. The data reported here are restricted to males. Feelings of boredom were associated with low adrenaline excretion rates. Reported physical tiredness was associated with low adrenaline levels, while mental tiredness seems to be related to high adrenaline levels. People who regarded themselves as having a competitive personality, as being faced by a large number of life challenges, as having to meet self-set deadlines, as choosing to focus on more than one task at the same time, or as being under time pressure had high rates. Cigarette smoking and coffee consumption were related to high adrenaline excretion rates. Taken together these variables can explain 16-20% of variance in adrenaline excretion. Smoking and coffee consumption are of primary importance. The results of similar analyses of noradrenaline are reported.

A DNA sequence obtained by replacement of the dopamine RNA aptamer bases is not an aptamer.

PubMed

Álvarez-Martos, Isabel; Ferapontova, Elena E

2017-08-05

A unique specificity of the aptamer-ligand biorecognition and binding facilitates bioanalysis and biosensor development, contributing to discrimination of structurally related molecules, such as dopamine and other catecholamine neurotransmitters. The aptamer sequence capable of specific binding of dopamine is a 57 nucleotides long RNA sequence reported in 1997 (Biochemistry, 1997, 36, 9726). Later, it was suggested that the DNA homologue of the RNA aptamer retains the specificity of dopamine binding (Biochem. Biophys. Res. Commun., 2009, 388, 732). Here, we show that the DNA sequence obtained by the replacement of the RNA aptamer bases for their DNA analogues is not able of specific biorecognition of dopamine, in contrast to the original RNA aptamer sequence. This DNA sequence binds dopamine and structurally related catecholamine neurotransmitters non-specifically, as any DNA sequence, and, thus, is not an aptamer and cannot be used neither for in vivo nor in situ analysis of dopamine in the presence of structurally related neurotransmitters. Copyright © 2017 Elsevier Inc. All rights reserved.

Clevidipine for hypertension treatment in pheochromocytoma surgery.

PubMed

Luis-García, C; Arbonés-Aran, E; Teixell-Aleu, C; Lorente-Poch, L; Trillo-Urrutia, L

2018-04-01

Pheochromocytoma is a catecholamine-producing tumour and laparoscopic adrenalectomy is its treatment of choice. During pneumoperitoneum insufflation and tumour handling there is a high risk of massive catecholamine release and hypertensive crisis. After tumour excision, severe arterial hypotension is a common effect, due to relative vasodilation and the residual effect of antihypertensive drugs. We report the case of a patient with pheochromocytoma who was treated with laparoscopic adrenalectomy. During surgical manipulation there was a sudden hypertensive peak that could be controlled quickly with clevidipine infusion. After tumour resection, clevidipine perfusion was stopped and there were no arterial hypotension episodes. Clevidipine is a new intravenous calcium antagonist with rapid onset of action and short half-life that has no residual effect and does not produce arterial hypotension after tumour resection. For these reasons, it can be a first-choice drug for this kind of surgery. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

PubMed

Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Abrupt withdrawal of beta-blocking agents in patients with arterial hypertension. Effect on blood pressure, heart rate and plasma catecholamines and prolactin.

PubMed

Lederballe Pedersen, O; Mikkelsen, E; Lanng Nielsen, J; Christensen, N J

1979-04-17

Chronic treatment with beta-blockers was interrupted abruptly in six patients with arterial hypertension. Three patients, who had experienced symptoms during a previous withdrawal, again complained of transient palpitations, tremor, sweating, headache and general malaise. A significant increase in standing blood pressure (BP) and heart rate (HR) was noted after 24 h. The standing HR reached a maximum after 48 h and had decreased significantly on the 7th day (p less than 0.005). There was a strong tendency to greater increase in standing BP and HR in the patients who experienced symptoms than in those who did not. Plasma concentrations of noradrenaline, adrenaline and prolactin did not change significantly. Thus, beta-blocker withdrawal symptoms are reproducible and are indicative of a transient sympathetic hyperresponse. The increased activity is not likely to be caused by increased production of circulating catecholamines, but rather by increased sensitivity of the beta-receptor.

CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)−mediated apoptosis

PubMed Central

Lee, Y Y; Moujalled, D; Doerflinger, M; Gangoda, L; Weston, R; Rahimi, A; de Alboran, I; Herold, M; Bouillet, P; Xu, Q; Gao, X; Du, X-J; Puthalakath, H

2013-01-01

Catecholamines regulate the β-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the β-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases. PMID:23579242

Memory dynamics under stress.

PubMed

Quaedflieg, Conny W E M; Schwabe, Lars

2018-03-01

Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.

Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women.

PubMed

Komesaroff, P A; Esler, M D; Sudhir, K

1999-02-01

Estrogens are reported to provide protection against the development of cardiovascular disease in women, but the mechanisms underlying these effects are not well defined. We hypothesized that estrogen might affect the hormonal responses to stress. We therefore studied cortisol, ACTH, epinephrine, norepinephrine, and norepinephrine spillover and hemodynamic responses to a 10-min mental arithmetic test in 12 perimenopausal women randomized to 8 weeks of estrogen supplementation (estradiol valerate, 2 mg daily; n = 7) or placebo (n = 5). Total body and forearm norepinephrine spillover were measured by radiotracer methodology. After supplementation with estradiol, the increases in both systolic and diastolic blood pressure in response to mental stress were reduced, and cortisol, ACTH, plasma epinephrine and norepinephrine, and total body norepinephrine spillover responses to stress were significantly attenuated (P < 0.05 in each case). Forearm norepinephrine spillover was unchanged by estrogen, and there was no change in any of the responses after placebo. We conclude that estrogen supplementation in perimenopausal women attenuates blood pressure, glucocorticoid, and catecholamine responses to psychological stress.

Activity of the sympathetic-adrenomedullary system in rats after space flight on the COSMOS biosatellites

NASA Astrophysics Data System (ADS)

Kvetňanský, R.; Vigaš, M.; Németh, Š.; Macho, L.; Tigranyan, R. A.

The indicators of adrenomedullary activity (catecholamine content (CA) and the activity of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH)) were measured in the adrenal glands of rats living in a state of weightlessness for 18.5-19.5 days on board the biosatellites COSMOS 936 and COSMOS 1129. None of these indicators was significantly changed by space flight, neither in the group living in a state of weightlessness nor in the group living in a centrifuge on board the spacecraft and exposed to artificial gravity of 1 g (COSMOS 936). Animals exposed after space flight to repeated immobilization stress on Earth showed a significant decrease of adrenal adrenaline and an appreciable increase in adrenal TH activity compared to stressed animals which were not in space. These results suggest that a prolonged state of weightlessness during space flight does not by itself represent an intensive stressful stimulus for the adrenomedullary system but potentiates the response of cosmonauts to stress after return to Earth.

Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

2011-01-01

Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

PubMed

Oliveira, Marcela Silva; Carmona, Fabio; Vicente, Walter V A; Manso, Paulo H; Mata, Karina M; Celes, Mara Rúbia; Campos, Erica C; Ramos, Simone G

2017-04-01

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β 1 , β 2 -adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β 1 and β 2 receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of β- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

Analysis of Stress Indicators for Evaluation of Animal Welfare and Meat Quality in Traditional and Jewish Slaughtering

PubMed Central

Barrasso, Roberta; Marchetti, Patrizia; Samoilis, Giorgio; Tantillo, Giuseppina; Ceci, Edmondo

2018-01-01

Simple Summary Cortisol and catecholamines (dopamine, norepinephrine and epinephrine) are released in response to stress and directly stimulate glycogen mobilization, thus influencing meat acidification. The aim of the study was to estimate and compare these stress indicators to evaluate the welfare of beef cattle, subjected to either traditional slaughtering (with stunning) or to slaughtering with religious Jewish rite (without stunning). Significant differences in plasma cortisol and catecholamine levels were observed during exsanguination by monitoring animals in the pre-slaughtering (before and after transportation) and slaughtering phases. Cortisol, dopamine and norepinephrine, but not epinephrine, were markedly higher in the animals slaughtered by the religious rite. Pursuing animal welfare in the religious slaughtering procedures could produce advantages in terms of hygiene, organoleptic quality and shelf life of meat. Abstract Sixty Charolais male beef cattle of eight months of age were divided into two groups according to the slaughtering method, i.e., traditional or Kosher (religious Jewish rite). The aim of the study was to detect and compare the plasma concentrations of cortisol and catecholamines (dopamine, norepinephrine and epinephrine), by Elisa and HPLC test. These four stress indicators were evaluated during three different stages of each animal productive life: on the farm (step 1), after transportation (step 2) and during bleeding (step 3). The patterns of the parameters measured were similar and, interestingly, revealed significant changes throughout the three steps considered. The greatest variation between the two methods of slaughtering was observed in step 3, where we found a statistically significant difference with all the parameters except epinephrine. In the animals slaughtered by the religious rite, cortisol, dopamine, norepinephrine and epinephrine were 68.70 ± 30.61 nmol/L; 868.43 ± 508.52 ng/L; 3776.20 ± 1918.44 ng/L; and 4352.20 ± 3730.15 ng/L, respectively, versus 45.08 ± 14.15 nmol/L; 513.87 ± 286.32 ng/L; 3425.57 ± 1777.39 ng/L; and 3279.97 ± 1954.53 ng/L, respectively, in the other animals. This suggests that the animals slaughtered by the Kosher rite are subjected to higher stress conditions at the exsanguination phase. The animals slaughtered by the religious Jewish rite showed lower cortisol and catecholamine levels on the farm (step 1) and after transportation to the slaughterhouse (step 2). This was likely because the animals selected at the end of step 1 by the Rabbis for the religious rite are usually the most docile and gentle. PMID:29561752

Stress and Simulation in Pilot Training. Final Report, May 1977 Through December 1977.

ERIC Educational Resources Information Center

Krahenbuhl, Gary S.; And Others

Research was conducted on pilot stress during simulated emergency flight conditions. Catecholamine (adrenaline and non-adrenaline) secretion for twenty United States Air Force student pilots and thirteen instructor pilots was determined during daily activities, during simulated flights performed in high realism simulators, and during actual…

Dissociation in Response to Methylphenidate on Response Variability in a Group of Medication Naive Children with ADHD

ERIC Educational Resources Information Center

Johnson, Katherine A.; Barry, Edwina; Bellgrove, Mark A.; Cox, Marie; Kelly, Simon P.; Daibhis, Aoife; Daly, Michael; Keavey, Michelle; Watchorn, Amy; Fitzgerald, Michael; McNicholas, Fiona; Kirley, Aiveen; Robertson, Ian H.; Gill, Michael

2008-01-01

Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to…

PERINATAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AROCLOR 1016 OR 1254 DID NOT ALTER BRAIN CATECHOLAMINES NOR DELAYED ALTERNATION PERFORMANCE IN LONG EVANS RATS

EPA Science Inventory

Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB ar...

An Experimental Brain Missile Wound: Ascertaining Pathophysiology and Evaluating Treatments to Lower Mortality and Morbidity

DTIC Science & Technology

1990-12-05

lidocaine ). An endotracheal tube smeared with topical anesthetic (2% xylocaine jelly) was inserted after application of local anesthetic (0.5 ml 2...methylepinephrine. Brain Res 235:271-283, 1982. 21 Huger F, Patrick G: Effect of concussive head injury on central catecholamine levels and synthesis rates in rat

Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

DTIC Science & Technology

2012-09-01

Treatment of Metastatic Pheochromocytoma PRINCIPAL INVESTIGATOR: Arthur S. Tischler...Treatment of Metastatic Pheochromocytoma 5a. CONTRACT NUMBER W81XWH-11-1-0670 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Pheochromocytomas (PCC) are catecholamine-producing neuroendocrine tumors. Up to 30% give

Catecholamine, Corticosteroid and Ketone Excretion in Exercise and Hypoxia,

DTIC Science & Technology

OHCS excretion tended to be higher during the experimental period and subsequently lower overnight during the hypoxia week. Ketosis occurred in two...subjects. In one of these it could be readily related to previous extraneous stress. Excretion of unidentified ketones in overnight urines was sometimes suspected and occurred beyond doubt following gross ketosis . (Author)

Melanin Biosynthesis in Cryptococcus neoformans

PubMed Central

Williamson, Peter R.; Wakamatsu, Kazumasa; Ito, Shosuke

1998-01-01

Pigment production by Cryptococcus neoformans is virulence associated. Dopamine- and 3,4-dihydroxyphenylalanine–melanin products were identified after acidic permanganate oxidation, alkaline hydrogen peroxide oxidation, or hydrolysis with hydriodic acid. These data provide direct chemical evidence for the formation of eumelanin polymers by catecholamine oxidation by laccase alone followed by oxidative coupling of dihydroxyindole. PMID:9515929

REPRODUCTIVE FUNCTIONS AND HYPOTHALAMIC CATECHOLAMINES IN RESPONSE TO THE SOIL FUMIGANT METAM SODIUM: ADAPTATIONS TO EXTENDED EXPOSURES

EPA Science Inventory

Metam sodium (MS) is a soil fumigant and Category II pesticide with a relatively low toxicity in mammals. Previous data have shown an ability to impair reproductive mechanisms in ovariectomized, estradiol-primed rats. A single i.p. injection blocked the luteinizing hormone (LH) s...

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines

PubMed Central

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock. PMID:29270582

Effects of acute exposure to WIFI signals (2.45GHz) on heart variability and blood pressure in Albinos rabbit.

PubMed

Saili, Linda; Hanini, Amel; Smirani, Chiraz; Azzouz, Ines; Azzouz, Amina; Sakly, Mohsen; Abdelmelek, Hafedh; Bouslama, Zihad

2015-09-01

Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter maximum amplitude and P waves. After intravenously injection of dopamine (0.50ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that, WIFI alter catecholamines (dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radiofrequency can act directly and/or indirectly on cardiovascular system. Copyright © 2015 Elsevier B.V. All rights reserved.

Angiotensin II in Refractory Septic Shock.

PubMed

Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

2017-05-01

Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

The TiPS/TINS lecture. Catecholamines: from gene regulation to neuropsychiatric disorders.

PubMed

Mallet, J

1996-04-01

In addition to their ability to change the electrical properties of neurones, evidence suggests that neurotransmitters are able to alter the cell's metabolism. Transmitter phenotype is labile and expression might be regulated, during development, by the cellular environment of neurones. The study of a key enzyme in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues about these adaptive responses. This enzyme has a large molecular diversity, resulting from the differential splicing of its mRNA, which is tissue-specific and might result in long-term changes in activity of the enzyme and, therefore, in the availability of neurotransmitter at various synapses. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain, including manic-depressive illness and schizophrenia. Indeed, an association between a rare variant allele of the gene encoding TH and the occurrence of schizophrenia has been found in several populations. New techniques being developed to treat diseases such as Parkinson's disease involve various gene therapies, including a method of transferring genes directly into nerve cells using an adenovirus-based system.

The TiPS/TINS Lecture. Catecholamines: from gene regulation to neuropsychiatric disorders.

PubMed

Mallet, J

1996-05-01

In addition to their ability to change the electrical properties of neurons, evidence suggests that neurotransmitters are able to alter the cell's metabolism. Transmitter phenotype is labile and expression might be regulated, during development, by the cellular environment of neurons. The study of a key enzyme in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues about these adaptive responses. This enzyme has a large molecular diversity, resulting from the differential splicing of its mRNA, which is tissue-specific and might result in long-term changes in activity of the enzyme and, therefore, in the availability of neurotransmitter at various synapses. The presence of different DNA sequences at the TH locus confers susceptibility to various disorders of the brain, including manic-depressive illness and schizophrenia. Indeed, an association between a rare variant allele of the gene encoding TH and the occurrence of schizophrenia has been found in several populations. New techniques being developed to treat diseases such as Parkinson's disease involve various gene therapies, including a method of transferring genes directly into nerve cells using an adenovirus-based system.

Phaeochromocytoma.

PubMed

Cryer, P E

1985-02-01

Phaeochromocytomas are uncommon among patients with hypertension, and sometimes occur in persons without known hypertension, but are important to detect because they are often lethal but commonly curable, and because they are a clue to the presence of associated conditions. Paroxysmal symptoms (especially headache, palpitations, diaphoresis and anxiety), hypertension that is intermittent, unusually labile or resistant to conventional therapy, and conditions known to be associated raise the clinical suspicion of phaeochromocytoma. Biochemical confirmation is commonly achieved by measurement of urinary catecholamines, metanephrines or VMA. Plasma noradrenaline and adrenaline measurements may be superior to measurements of urinary catecholamine metabolites, but strict attention to the details of sample collection, handling and storage, the many sources of possible biological variation and the effects of drugs is critical if diagnostic error is to be avoided. Patients should be evaluated in the drug-free state if at all possible. Anatomical localization, in the abdomen in the vast majority of cases and usually in the adrenal medullae, can generally be accomplished with computed tomographic scans. Bilateral adrenomedullary tumours are the rule in familial phaeochromocytoma. Most phaeochromocytomas are benign and can be excised totally after medical preparation with an alpha-adrenergic antagonist.

Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a water-soluble forskolin derivative, compared with those of isoproterenol, dopamine and dobutamine.

PubMed

Yoneyama, Masahiko; Sugiyama, Atsushi; Satoh, Yoshioki; Takahara, Akira; Nakamura, Yuji; Hashimoto, Keitaro

2002-12-01

Colforsin daropate is a recently developed water-soluble derivative of forskolin that directly stimulates adenylate cyclase, unlike the catecholamines. The chronotropic, inotropic and coronary vasodilator actions of colforsin daropate were compared with those of isoproterenol, dopamine and dobutamine, using canine isolated, blood-perfused heart preparations. The stimulating effect of each drug on adenylate cyclase activity was also assessed. Colforsin daropate, as well as each of the catecholamines, exerted positive chronotropic, inotropic and coronary vasodilator actions. The order of selectivity for the cardiovascular variables of colforsin daropate was coronary vasodilation > positive inotropy > positive chronotropy; whereas that of isoproterenol, dopamine and dobutamine was positive inotropy > coronary vasodilation > positive chronotropy. Thus, a marked characteristic of colforsin daropate is its potent coronary vasodilator action. On the other hand, each drug significantly increased the adenylate cyclase activity in a dose-related manner: colforsin daropate > isoproterenol > dopamine = dobutamine. These results suggest that colforsin daropate may be preferable in the treatment of severe heart failure where the coronary blood flow is reduced and beta-adrenoceptor-dependent signal transduction pathway is down-regulated.

Catecholamine plasma levels, IFN-γ serum levels and antibodies production induced by rabies vaccine in dogs selected for their paw preference.

PubMed

Siniscalchi, Marcello; Cirone, Francesco; Guaricci, Antonio Ciro; Quaranta, Angelo

2014-01-01

To explore the possible role of the sympathetic nervous activity in the asymmetrical crosstalk between the brain and immune system, catecholamine (E, NE) plasma levels, Interferon-γ (IFN-γ) serum levels and production of antibodies induced by rabies vaccine in dogs selected for their paw preference were measured. The results showed that the direction of behavioural lateralization influenced both epinephrine levels and immune response in dogs. A different kinetic of epinephrine levels after immunization was observed in left-pawed dogs compared to both right-pawed and ambidextrous dogs. The titers of antirabies antibodies were lower in left-pawed dogs than in right-pawed and ambidextrous dogs. Similarly, the IFN-γ serum levels were lower in left-pawed dogs than in the other two groups. Taken together, these findings showed that the left-pawed group appeared to be consistently the different group stressing the fundamental role played by the sympathetic nervous system as a mechanistic basis for the crosstalk between the brain and the immune system.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

PubMed

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

Neurocardiology: Therapeutic Implications for Cardiovascular Disease

PubMed Central

Goldstein, David S.

2016-01-01

SUMMARY The term “neurocardiology” refers to physiologic and pathophysiological interplays of the nervous and cardiovascular systems. This selective review provides an update about cardiovascular therapeutic implications of neurocardiology, with emphasis on disorders involving primary or secondary abnormalities of catecholamine systems. Concepts of scientific integrative medicine help understand these disorders. Scientific integrative medicine is not a treatment method or discipline but a way of thinking that applies systems concepts to acute and chronic disorders of regulation. Some of these concepts include stability by negative feedback regulation, multiple effectors, effector sharing, instability by positive feedback loops, allostasis, and allostatic load. Scientific integrative medicine builds on systems biology but is also distinct in several ways. A large variety of drugs and non-drug treatments are now available or under study for neurocardiologic disorders in which catecholamine systems are hyperfunctional or hypofunctional. The future of therapeutics in neurocardiology is not so much in new curative drugs as in applying scientific integrative medical ideas that take into account concurrent chronic degenerative disorders and interactions of multiple drug and non-drug treatments with each other and with those disorders. PMID:21108771

Additional Antiepileptic Mechanisms of Levetiracetam in Lithium-Pilocarpine Treated Rats

PubMed Central

Al-Shorbagy, Muhammad Y.; El Sayeh, Bahia M.; Abdallah, Dalaal M.

2013-01-01

Several studies have addressed the antiepileptic mechanisms of levetiracetam (LEV); however, its effect on catecholamines and the inflammatory mediators that play a role in epilepsy remain elusive. In the current work, lithium (Li) pretreated animals were administered LEV (500 mg/kg i.p) 30 min before the induction of convulsions by pilocarpine (PIL). Li-PIL-induced seizures were accompanied by increased levels of hippocampal prostaglandin (PG) E2, myeloperoxidase (MPO), tumor necrosis factor-α, and interleukin-10. Moreover, it markedly elevated hippocampal lipid peroxides and nitric oxide levels, while it inhibited the glutathione content. Li-PIL also reduced hippocampal noradrenaline, as well as dopamine contents. Pretreatment with LEV protected against Li-PIL-induced seizures, where it suppressed the severity and delayed the onset of seizures in Li-PIL treated rats. Moreover, LEV reduced PGE2 and MPO, yet it did not affect the level of both cytokines in the hippocampus. LEV also normalized hippocampal noradrenaline, dopamine, glutathione, lipid peroxides, and nitric oxide contents. In conclusion, alongside its antioxidant property, LEV anticonvulsive effect involves catecholamines restoration, as well as inhibition of PGE2, MPO, and nitric oxide. PMID:24098559

Electroconvulsive therapy for depression following acute coronary syndromes: a concern for the anesthesiologist.

PubMed

Pourafkari, Nosratollah; Pourafkari, Leili; Nader, Nader D

2016-06-01

The prevalence of depression in patients with cardiovascular disease is higher than general population and especially following an acute coronary syndrome (ACS), a significant number of patients report a wide spectrum of behavioral and mood changes attributable to clinical depression. Treatment of depression following ACS event is particularly challenging since most of the therapeutic modalities are associated with increasing the systemic sympathetic tone from neurogenic or pharmacologic sources. Increased activity of the adrenergic and catecholamine activity may further deter the myocardial oxygen supply and demand therefore treating depression should be carefully evaluated for its risk benefit ratio. Electroconvulsive therapy (ECT) is recommended for patients with severe depression, in whom behavioral and pharmacologic treatments have failed. Patients who refuse to take medications or present with any psychological emergency such as harming self or others, are also candidates for ECT. ECT is also associated with sudden surges of catecholamines and may cause recurrent myocardial ischemia and fatal dysrhythmias in patients convalescing from an ACS event. Herein, we provide an overview and practical guidelines for management of patients presented for ECT following ACS. Published by Elsevier Inc.

Allelic variation in dopamine D2 receptor gene is associated with attentional impulsiveness on the Barratt Impulsiveness Scale (BIS-11).

PubMed

Taylor, Jasmine B; Cummins, Tarrant D R; Fox, Allison M; Johnson, Beth P; Tong, Janette H; Visser, Troy A W; Hawi, Ziarih; Bellgrove, Mark A

2017-01-20

Previous studies have postulated that noradrenergic and/or dopaminergic gene variations are likely to underlie individual differences in impulsiveness, however, few have shown this. The current study examined the relationship between catecholamine gene variants and self-reported impulsivity, as measured by the Barratt Impulsiveness Scale (Version 11; BIS-11) Methods: Six hundred and seventy-seven non-clinical adults completed the Barratt Impulsiveness Scale (BIS-11). DNA was analysed for a set of 142 single-nucleotide polymorphisms (SNPs) across 20 autosomal catecholamine genes. Association was tested using an additive regression model with permutation testing used to control for the influence of multiple comparison. Analysis revealed an influence of rs4245146 of the dopamine D2 receptor (DRD2) gene on the BIS-11 attention first-order factor, such that self-reported attentional impulsiveness increased in an additive fashion with each copy of the T allele. These findings provide preliminary evidence that allelic variation in DRD2 may influence impulsiveness by increasing the propensity for attentional lapses.

Monoamine oxidases as sources of oxidants in the heart

PubMed Central

Kaludercic, Nina; Mialet-Perez, Jeanne; Paolocci, Nazareno; Parini, Angelo; Di Lisa, Fabio

2014-01-01

Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidases (MAO) have been described as a prominent source. MAO are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generate H2O2 and aldehyde intermediates. The role of MAO in cardiovascular pathophysiology has only recently gathered some attention since it has been demonstrated that both H2O2 and aldehydes may target mitochondrial function and consequently affect function and viability of the myocardium. In the present review, we will discuss the role of MAO in catecholamine and serotonin clearance and cycling in relation to cardiac structure and function. The relevant contribution of each MAO isoform (MAO-A or -B) will be discussed in relation to mitochondrial dysfunction and myocardial injury. Finally, we will examine both beneficial effects of their pharmacological or genetic inhibition along with potential adverse effects observed at baseline in MAO knockout mice, as well as the deleterious effects following their over-expression specifically at cardiomyocyte level. PMID:24412580

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

PubMed

Kato, Eisuke; Kimura, Shunsuke; Kawabata, Jun

2017-12-15

β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.

PubMed

Ciszek, Brittney P; O'Buckley, Sandra C; Nackley, Andrea G

2016-05-01

Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486. The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.

Poly(dimethylsiloxane) cross-linked carbon paste electrodes for microfluidic electrochemical sensing.

PubMed

Sameenoi, Yupaporn; Mensack, Meghan M; Boonsong, Kanokporn; Ewing, Rebecca; Dungchai, Wijitar; Chailapakul, Orawan; Cropek, Donald M; Henry, Charles S

2011-08-07

Recently, the development of electrochemical biosensors as part of microfluidic devices has garnered a great deal of attention because of the small instrument size and portability afforded by the integration of electrochemistry in microfluidic systems. Electrode fabrication, however, has proven to be a major obstacle in the field. Here, an alternative method to create integrated, low cost, robust, patternable carbon paste electrodes (CPEs) for microfluidic devices is presented. The new CPEs are composed of graphite powder and a binder consisting of a mixture of poly(dimethylsiloxane) (PDMS) and mineral oil. The electrodes are made by filling channels molded in previously cross-linked PDMS using a method analogous to screen printing. The optimal binder composition was investigated to obtain electrodes that were physically robust and performed well electrochemically. After studying the basic electrochemistry, the PDMS-oil CPEs were modified with multi-walled carbon nanotubes (MWCNT) and cobalt phthalocyanine (CoPC) for the detection of catecholamines and thiols, respectively, to demonstrate the ease of electrode chemical modification. Significant improvement of analyte signal detection was observed from both types of modified CPEs. A nearly 2-fold improvement in the electrochemical signal for 100 μM dithiothreitol (DTT) was observed when using a CoPC modified electrode (4.0 ± 0.2 nA (n = 3) versus 2.5 ± 0.2 nA (n = 3)). The improvement in signal was even more pronounced when looking at catecholamines, namely dopamine, using MWCNT modified CPEs. In this case, an order of magnitude improvement in limit of detection was observed for dopamine when using the MWCNT modified CPEs (50 nM versus 500 nM). CoPC modified CPEs were successfully used to detect thiols in red blood cell lysate while MWCNT modified CPEs were used to monitor temporal changes in catecholamine release from PC12 cells following stimulation with potassium.

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

PubMed Central

Koulu, M; Scheinin, M; Kaarttinen, A; Kallio, J; Pyykkö, K; Vuorinen, J; Zimmer, R H

1989-01-01

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. PMID:2469451

Phaeochromocytoma: state-of-the-art.

PubMed

Donckier, J E; Michel, L

2010-01-01

Phaeochromocytomas are catecholamine-secreting tumours that arise from chromaffin cells of the adrenal medulla and extra-adrenal sites. Extra-adrenal phaeochromocytomas are called paragangliomas. A diagnosis of phaeochromocytoma is suspected by typical paroxysmal symptoms, unusual or refractory hypertension, discovery of an adrenal incidentaloma or a family history of phaeochromocytoma or paraganglioma, possibly associated with other genetic syndromes (multiple endocrine neoplasia type 2 A or B, neurofibromatosis type 1 and von Hippel-Lindau disease). It can be confirmed by measurements of urinary or plasma fractionated catecholamines and metanephrines. The best diagnostic performances are achieved by metanephrines. Twenty-four hour urine fractionated metanephrines are still recommended as a screening test but some experts prefer plasma measurements in high-risk patients. Increased serum chromogranin-A levels, combined with high catecholamine or metanephrine in a patient with normal renal function is also a tool, virtually diagnostic of phaeochromocytoma. Recent studies have suggested that 25% of patients with phaeochromocytoma have germline mutations of several genes (NF1, VHL, SDHD, SDHB and RET). Thus, genetic testing should be carried out according to an algorithm of risk factors and specific characteristics. Once a biochemical diagnosis of phaeochromocytoma is made, a CT scan or MRI of the abdomen and pelvis should be performed first. If these investigations remain negative, the chest and neck should be explored. After anatomical imaging, functional imaging by 123I-MIBG should be considered. If the MIBG scan is negative, other imaging modalities have recently proven to be useful (PET, Octreoscan). After localization, the treatment of phaeochromocytoma is a surgical resection, which may be laparoscopic. Preoperative preparation with alpha- and beta-adrenergic blockade and/or calcium channel blockers associated with volume expansion is essential. Malignant phaeochromocytoma is rare and its treatment still unsatisfying. Phaeochromocytoma during pregnancy is also rare and its diagnosis easily missed because of its clinical resemblance to pre-eclampsia.

Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress☆

PubMed Central

Hanke, M.L.; Powell, N.D.; Stiner, L.M.; Bailey, M.T.; Sheridan, J.F.

2012-01-01

During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic–pituitary–adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b+ splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18 h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b+ cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation. PMID:22841997

Pheochromocytoma of the Organ Zuckerkandl.

PubMed

Lee, C; Chang, E; Gimenez, J; McCarron, R

2017-01-01

Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);, are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal paragangliomas may arise in the sympathetic or parasympathetic paraganglia and more rarely in other organs. One of the most common extra-adrenal sites is in the organ of Zuckerkandl, a collection of chromaffin cells near the origin of the inferior mesenteric artery or near the aortic bifurcation. The following is a case of a patient with resistant hypertension secondary to an extra-adrenal paraganglioma in the organ of Zuckerkandl. The patient is a 43 year old man with a history of depression, type 2 diabetes mellitus, and hypertension who was sent to the emergency department by his primary care physician for severely elevated blood pressures. Patient also had diaphoresis, tachycardia, and a new, fine tremor of his left hand. Upon presentation, the patient's blood pressure was 260/120 mmHg with a heart rate of 140 beats per minute. Plasma fractionated metanephrines sent on admission revealed significantly elevated levels of total plasma metanephrines (2558 pg/mL);, free metanephrine (74 pg/ml); and free normetanephrine (2484pg/mL);. An I-123 metaiodobenzylguanidine (MIBG); scan showed abnormal uptake in the lower abdomen at the level of the aortic bifurcation. Patient was started on alpha-blockade, with subsequent addition of a beta-blocker prior to surgery. Patient underwent surgical removal of the tumor with pathology consistent with a paraganglioma. Pheochromocytomas and paragangliomas are responsible for approximately 0.5 percent of cases of secondary hypertension. Many different biochemical markers have been used to aid in the diagnosis of PCC/PGL including plasma catecholamines, plasma metanephrines, urine fractionated metanephrines, urine catecholamines, total metanephrines and vanillymandellic acid. Definitive management of a PCC and PGL involves surgical removal of the tumor. Finally, there should be a discussion with each patient to determine if he or she should undergo genetic testing, as studies show that approximately 25 percent of catecholamine producing PCCs and PGLs are due to heritable genetic mutations.

Fluorescence histochemical and elec-ron microscopical observations on sympathetic ganglia of the chick embryo cultured with and without hydrocortisone.

PubMed

Hervonen, H; Eränkö, O

1975-01-01

Lumbar sympathetic ganglia of 12-day-old chick embryos were cultured in organ cultures for 14 days with 1, 10 or 100 mg/l of hydrocortisone or without it. Catecholamines were demonstrated by the formaldehyde-induced fluorescence method. For electron microscopy, the cultures were fixed with glutarialdehyde and osmium tetroxide. Two types of cells with catecholamine fluoresecence were observed in the control cultures: (1) weakly fluorescent sympathetic neurons and sympathicoblasts with long nerve fibres, which were the most common cell type in the explant, and (2) brightly fluorescent cells with or without fluorescent processes, which were less common and were scattered in the explant. Hydrocortisone caused a great increase in the number of the brightly fluorescent cells. With 10 mg/l of hydrocortisone the increase was about ten-fold as compared with the control cultures. There was no change in the morphology of the cells, nor could any change be observed in the fluorescence intensity by eye. Electron microscopically the mature neurons were the most common cell type on the surface of the culture, while more immature sympathicoblasts were seen in the deeper layers. Cells were also found which contained large numbers of catecholamine-strong granular vesicles 105-275 nm in diameter. These cells were infrequent. They had round vesicular nuclei and resembled also in other respects sympathicoblasts or young nerve cells. One such cell was found in mitotic division by electron microscopy. Hydrocortisone caused a marked increase in the number of these granule-containing cells and their processes. Cells which could have been classified as the small intensely fluorescent cells of the mammalian ganglion type or their electron microscopic equivalent, the granule-containing cells were found neither in the control cultures nor in the hydrocortisone-containing cultures. It is concluded that most brightly fluorescent cells in cultured sympathetic ganglia of the chick are nerve cells or sympathicoblasts rich in amine-storing granular vesicles.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

PubMed

Zueger, Thomas; Loher, Hannah; Egger, Andrea; Boesch, Chris; Christ, Emanuel

2016-08-01

Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

PubMed

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015).

PubMed

Miklya, I

2016-11-01

Deprenyl/Selegiline (DEP), created by Joseph Knoll in the 1960s, registered in more than 60 countries to treat Parkinson's disease, Alzheimer's disease, major depressive disorder; and used as an anti-aging drug, achieved its place in research and therapy as the first selective inhibitor of B-type monoamine oxidase (MAO-B). The demonstration that the DEP analog (-)-1-phenyl-2-propylaminopentane devoid of MAO inhibitory property, enhanced like DEP the activity of the catecholaminergic brain engine revealed that this effect is unrelated to the selective inhibition of MAO-B. β-Phenylethylamine (PEA), the important trace-amine in the mammalian brain, is known to be a releaser of catecholamines. Amphetamine and methamphetamine, the best known synthetic PEA derivatives are also releasers of catecholamines like their parent compound. DEP is a unique synthetic PEA derivative devoid of the catecholamine releasing property. As the releasing effect conceals the catecholaminergic activity enhancer (CAE) effect, it remained undiscovered until DEP uncovered that PEA is a natural CAE substance; and only releases catecholamines in high concentration. Discovering that tryptamine is a natural enhancer of catecholaminergic and serotonergic neurons catalyzed the development of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane (BPAP); the most potent and selective enhancer substance, and it exerts its enhancer effect in 0.0001 mg kg -1 . DEP and BPAP initiated an analysis of the enhancer regulation in the mammalian brain. Studies regarding the nature of the enhancer regulation revealed that this regulation is enhanced after weaning and sex hormones return it to the pre-weaning level. Thus, sex hormones elicit the transition of the developmental phase of life into the post-developmental, downhill (aging) period. The aging-related, slow decline in the enhancer regulation of the catecholaminergic brain engine, the main activator of the cortex, is the prime factor of brain aging. The enhancer regulation's decay in the most rapidly aging dopaminergic system is, for example, mainly responsible for the decline in learning ability and sexual activity over time. According to the Knoll concept, based on two longevity studies performed on male rats, to keep the catecholaminergic brain engine, from the beginning of the downhill period of life, via the administration of a small daily dose of a CAE substance (presently DEP is the only available drug) on a higher activity level, thus to fight against the physiological aging-related slow decay of the catecholaminergic system, is a suitable anti-aging therapy. As our present knowledge regarding the enhancer regulation in the mammalian brain is like seeing a peak of an iceberg, the future of this new line of brain research looks promising from both theoretical and practical aspects.

A Preliminary Study of Gene Polymorphisms Involved in the Neurotransmitters Metabolism of a Homogeneous Spanish Autistic Group

ERIC Educational Resources Information Center

Calahorro, Fernando; Alejandre, Encarna; Anaya, Nuria; Guijarro, Teresa; Sanz, Yolanza; Romero, Auxiliadora; Tienda, Pilar; Burgos, Rafael; Gay, Eudoxia; Sanchez, Vicente; Ruiz-Rubio, Manuel

2009-01-01

Twin studies have shown a strong genetic component for autism. Neurotransmitters, such as serotonin and catecholamines, have been suggested to play a role in the disease since they have an essential function in synaptogenesis and brain development. In this preliminary study, polymorphism of genes implicated in the serotonergic and dopaminergic…

Measures of Self-Report, Urinary Catecholamines, and Salivary Immunoglobulin-A in Victims of Chronic Stress

DTIC Science & Technology

1985-05-22

suggesting T cell deficiency £rom thymectomy decreased host •l lilllil .’! resistance to tumors<Comsa & Hook, 1973; Prehn , 1969>. l!ll~lll...environment. American Journal of Psychiatry, 1974, 131, 651-654. Prehn , R.T. The relationship o£ immunology to carcinogenesis. Annals of the New York

The Salmonella enterica serovar Typhimurium QseB Response Regulator Negatively Regulates Bacterial Motility and Swine Colonization in the Absence of the QseC Sensor Kinase

USDA-ARS?s Scientific Manuscript database

Salmonella enterica serovar Typhimurium (S. Typhimurium) responds to the catecholamine, norepinephrine by increasing bacterial growth and enhancing motility. In this study, iron with or without the siderophore, ferrioxamine E also enhanced bacterial motility. Iron-enhanced motility was growth-rate ...

Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

EPA Science Inventory

In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

Ouabain-sensitive component of brown fat thermogenesis.

NASA Technical Reports Server (NTRS)

Horwitz, B. A.

1973-01-01

The study discussed was undertaken to quantify the amount of energy utilized by the ouabain-sensitive Na(+)-K(+) membrane pump during the norepinephrine-induced thermogenesis of brown adipose tissue. The data obtained indicate that the observed inhibition of the catecholamine-induced increase in brown fat thermogenesis by ouabain does not reflect an inhibition of cyclic AMP synthesis.

The aromatic amino acid hydroxylase genes AAH1 and AAH2 in Toxoplasma gondii contribute to transmission in the cat

USDA-ARS?s Scientific Manuscript database

The Toxoplasma gondii genome contains two aromatic amino acid hydroxylase genes, AAH1 and AAH2, which encode proteins that produce L-DOPA, which can serve as a precursor of catecholamine neurotransmitters. It has been suggested that this pathway elevates host dopamine levels thus making infected rod...

Variability of Hormonal Stress Markers Collected from a Managed Dolphin Population

DTIC Science & Technology

2011-09-30

physiological indicators of stress in wild marine mammals and the interrelationships between different stress markers can be used to estimate the impact of...samples will be processed for adrenocorticosteroids (ACTH, cortisol, aldosterone ), catecholamines (epinephrine, norepinephrine), and thyroid hormones...T3 and T4) via radioimmunoassay (RIA). Radioimmunoassay methods have previously been validated for cortisol and aldosterone in this species (Houser

Pheochromocytoma of urinary bladder - a case report.

PubMed

Sharma, Shaleen; Gokhro, Sunil; Sharma, K K; Sadasukhi, T C

2007-08-01

Pheochromocytomas are catecholamine producing neuroendocrine tumours. Bladder involvement with pheochromocytoma is rare that usually presents with hypertension, hematuria and syncope often related to voiding. Clinical manifestation may be inconsistent and high index of suspicion is required for accurate diagnosis. We report a case, who presented with gross intermittent hematuria and mild elevation of pulserate and bloodpressure. Patient was adequately treated with partial cystectomy.

Circulating catecholamine and glucose concentrations in Japanese toads (Bufo japonicus) during the breeding season.

PubMed

Wilson, J X; Sawai, H; Kikuchi, M; Kubokawa, K; Ishii, S

1995-06-01

We investigated the relationship between catecholamine neurohormones and glucose during seasonal reproductive activity in Japanese toads (Bufo japonicus). Field studies found that plasma epinephrine concentration increased as toads migrated to their breeding ponds, where amplexus most frequently took place. Blood glucose concentration also increased as toads arrived at the ponds, even though these animals did not eat during the breeding season, and there was a positive correlation between epinephrine and glucose levels. Blood glucose concentration was higher in amplectic than in solitary males, whereas this relationship did not occur in females. For both males and females, plasma epinephrine concentration was elevated during amplexus. The plasma concentration of norepinephrine was lower than that of epinephrine and did not correlate with either the proximity of the animal to the breeding ponds or the blood glucose concentration. Laboratory experiments showed that systemic injection of [Trp7,Leu8]gonadotropin-releasing hormone (sGnRH) increased plasma epinephrine to levels characteristic of amplectic feral toads. These results suggest that a physiological role of GnRH-like peptides may be to stimulate epinephrine secretion and consequently to increase glucose production in toads under the starvation conditions associated with the breeding migration.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

PubMed

Ferreira, Jason A; Bissell, Brittany D

2018-02-01

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective β-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Adrenal haemangioblastoma presenting as phaeochromocytoma: a rare manifestation of extraneural hemangioblastoma.

PubMed

Deb, Prabal; Pal, Seerat; Dutta, Vibha; Srivastava, Anand; Bhargava, Akshay; Yadav, Krishan Kumar

2012-09-01

Adrenal haemangioblastoma presenting clinically as pheochromocytoma is a rare manifestation of extraneural haemangioblastoma. We present an unusual case of von Hippel-Lindau (VHL) disease that had adrenal and cerebellar haemangioblastoma with multiple renal cysts, and a review of the literature. Unlike the usual manifestations of secondary polycythemia or increased intracranial pressure and hydrocephalus due to cerebellar lesion, this 36-year-old male presented with hypertension. Investigations revealed right suprarenal mass with raised urinary catecholamines and serum vanillylmandelic acid (VMA) levels, apparently confirming the clinical diagnosis of phaeochromocytoma. Histopathology of the biopsy specimen showed features of haemangioblastoma, which was confirmed by immunohistochemistry using antibodies to neuron specific enolase and aquaporin-1. Based on this, the patient was screened for possible features of VHL, which revealed cerebellar haemangioblastoma and multiple renal cysts with angiomatous lesion. Postoperative follow-up showed normal levels of catecholamines without any symptoms of phaeochromocytoma. Adrenal haemangioblastoma is a rare entity with only four cases reported in the literature. Surgical removal is the treatment of choice. However, screening for other possible features of VHL, even in the absence of clinical features, is essential to exclude other potential lesions.

Interactions Between Bacteria and the Gut Mucosa: Do Enteric Neurotransmitters Acting on the Mucosal Epithelium Influence Intestinal Colonization or Infection?

PubMed

Green, Benedict T; Brown, David R

2016-01-01

The intestinal epithelium is a critical barrier between the internal and external milieux of the mammalian host. Epithelial interactions between these two host environments have been shown to be modulated by several different, cross-communicating cell types residing in the gut mucosa. These include enteric neurons, whose activity is influenced by bacterial pathogens, and their secreted products. Neurotransmitters appear to influence epithelial associations with bacteria in the intestinal lumen. For example, internalization of Salmonella enterica and Escherichia coli O157:H7 into the Peyer's patch mucosa of the small intestine is altered after the inhibition of neural activity with saxitoxin, a neuronal sodium channel blocker. Catecholamine neurotransmitters, such as dopamine and norepinephrine, also alter bacterial internalization in Peyer's patches. In the large intestine, norepinephrine increases the mucosal adherence of E. coli. These neurotransmitter actions are mediated by well-defined catecholamine receptors situated on the basolateral membranes of epithelial cells rather than through direct interactions with luminal bacteria. Investigations of the involvement of neuroepithelial communication in the regulation of interactions between the intestinal mucosa and luminal bacteria will provide novel insights into the mechanisms underlying bacterial colonization and pathogenesis at mucosal surfaces.

Thermodynamic and kinetic analysis of the reaction between biological catecholamines and chlorinated methylperoxy radicals

NASA Astrophysics Data System (ADS)

Dimić, Dušan S.; Milenković, Dejan A.; Marković, Jasmina M. Dimitrić; Marković, Zoran S.

2018-05-01

The antiradical potency of catecholamines (dopamine, epinephrine, norepinephrine, L-DOPA), metabolites of dopamine (homovanillic acid, 3-methoxytyramine and 3,4-dihydroxyphenylacetic acid) and catechol towards substituted methylperoxy radicals is investigated. The thermodynamic parameters, together with the kinetic approach, are used to determine the most probable mechanism of action. The natural bond orbital and quantum theory of atoms in molecules are utilised to explain the highest reactivity of trichloromethylperoxy radical. The preferred mechanism is dependent both on the thermodynamic and kinetic parameters . The number of chlorine atoms on radical, the presence of intra-molecular hydrogen bond and number of hydroxy groups attached to the aromatic ring significantly influence the mechanism. The results suggest that sequential proton loss electron transfer (SPLET) is the most probable for reaction with methylperoxy and hydrogen atom transfer (HAT) for reaction with trichloromethylperoxy radicals, with a gradual transition between SPLET and HAT for other two radicals. Due to the significant deprotonation of molecules containing the carboxyl group, the respective anions are also investigated. The HAT and SPLET mechanisms are highly competitive in reaction with MP radical, while the dominant mechanism towards chlorinated radicals is HAT. The reactions in methanol and benzene are also discussed.

Mechanisms involved in the adaptations of the adipocyte adrenergic signal-transduction system and their modulation by growth hormone during the lactation cycle in the rat.

PubMed Central

Vernon, R G; Piperova, L; Watt, P W; Finley, E; Lindsay-Watt, S

1993-01-01

The mechanisms responsible for the diminished lipolytic response of adipocytes to catecholamines after litter removal from lactating rats and their modulation by growth hormone have been investigated. Lactation, litter removal and growth-hormone treatment did not alter the ability of noradrenaline to activate protein kinase A (A-kinase), showing that the defect in signal transduction in rats after litter removal is after A-kinase. Litter removal had no effect on hormone-sensitive lipase activity itself, but the proportion of the lipase associated with the fat droplet was decreased; growth-hormone treatment increased hormone-sensitive lipase activity and the proportion associated with the fat droplet. In addition, a number of other adaptations in the beta-adrenergic signal-transduction system occur during the lactation cycle and in response to growth hormone treatment, including changes in receptor number, adenylate cyclase activity and cyclic AMP phosphodiesterase activity, but a defect in the ability of hormone-sensitive lipase to associate with the lipid droplet appears to be the major reason for the diminished response to catecholamines on litter removal. PMID:8382054

Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs.

PubMed

Ufnal, Marcin; Skrzypecki, Janusz

2014-04-01

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Catecholamine exocytosis during low frequency stimulation in mouse adrenal chromaffin cells is primarily asynchronous and controlled by the novel mechanism of Ca2+ syntilla suppression

PubMed Central

Lefkowitz, Jason J; DeCrescenzo, Valerie; Duan, Kailai; Bellve, Karl D; Fogarty, Kevin E; Walsh, John V; ZhuGe, Ronghua

2014-01-01

Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate action potentials (APs) at a frequency near 0.5 Hz in the resting physiological state, at times described as ‘rest and digest’. How such low frequency stimulation in turn elicits sufficient catecholamine exocytosis to set basal sympathetic tone is not readily explained by the classical mechanism of stimulus–secretion coupling, where exocytosis is synchronized to AP-induced Ca2+ influx. By using simulated action potentials (sAPs) at 0.5 Hz in isolated patch-clamped mouse ACCs, we show here that less than 10% of all catecholaminergic exocytosis, measured by carbon fibre amperometry, is synchronized to an AP. The asynchronous phase, the dominant phase, of exocytosis does not require Ca2+ influx. Furthermore, increased asynchronous exocytosis is accompanied by an AP-dependent decrease in frequency of Ca2+ syntillas (i.e. transient, focal Ca2+ release from internal stores) and is ryanodine sensitive. We propose a mechanism of disinhibition, wherein APs suppress Ca2+ syntillas, which themselves inhibit exocytosis as they do in the case of spontaneous catecholaminergic exocytosis. PMID:25128575

Haloperidol response and plasma catecholamines and their metabolites.

PubMed

Green, A I; Alam, M Y; Boshes, R A; Waternaux, C; Pappalardo, K M; Fitzgibbon, M E; Tsuang, M T; Schildkraut, J J

1993-06-01

Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

Neuroenhancement of Exposure Therapy in Anxiety Disorders

PubMed Central

Hofmann, Stefan G.; Mundy, Elizabeth A.; Curtiss, Joshua

2015-01-01

Although exposure-based treatments and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Interestingly, combining these two modalities is usually not more effective than the monotherapies. Recent translational research has identified a number of novel approaches for treating anxiety disorders using agents that serve as neuroenhancers (also known as cognitive enhancers). Several of these agents have been studied to determine their efficacy at improving treatment outcome for patients with anxiety and other psychiatric disorders. In this review, we examine d-cycloserine, yohimbine, cortisol, catecholamines, oxytocin, modafinil, and nutrients such as caffeine and amino fatty acids as potential neuroenhancers. Of these agents, d-cycloserine shows the most promise as an effective neuroenhancer for extinction learning and exposure therapy. Yet, the optimal dosing and dose timing for drug administration remains uncertain. There is partial support for cortisol, catecholamines, yohimbine and oxytocin for improving extinction learning and exposure therapy. There is less evidence to indicate that modafinil and nutrients such as caffeine and amino fatty acids are effective neuroenhancers. More research is needed to determine their long term efficacy and clinical utility of these agents. PMID:26306326

The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

PubMed Central

Petidis, Konstantinos; Douma, Stella; Doumas, Michael; Basagiannis, Ilias; Vogiatzis, Konstantinos; Zamboulis, Chrysanthos

2008-01-01

Background Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function. Methods Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A2, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise. Results Our results during exercise showed a) platelet activation (increased thromboxane B2, TXB2), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups). Conclusion Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB2 levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications. PMID:18505546

Halloysite clay nanotubes and platinum nanoparticles dispersed in ionic liquid applied in the development of a catecholamine biosensor.

PubMed

Brondani, Daniela; Scheeren, Carla Weber; Dupont, Jairton; Vieira, Iolanda Cruz

2012-08-21

Halloysite clay nanotubes were used as a support for the immobilization of the enzyme peroxidase from clover sprouts (Trifolium), and employed together with platinum nanoparticles in 1-butyl-3-methylimidazolium hexafluorophosphate ionic liquid (Pt-BMI·PF(6)) in the development of a new biosensor for the determination of catecholamines by square-wave voltammetry. Under optimized conditions, the analytical curves showed detection limits of 0.05, 0.06, 0.07, 0.12 μM for dopamine, isoproterenol, dobutamine and epinephrine, respectively. The biosensor demonstrated high sensitivity, good repeatability and reproducibility, and long-term stability (18% decrease in response over 150 days). A recovery study of dopamine in pharmaceutical samples gave values from 97.5 to 101.4%. The proposed biosensor was successfully applied to the determination of dopamine in pharmaceutical samples, with a maximum relative error of ±1.0% in relation to the standard (spectrophotometric) method. The good analytical performance of the proposed method can be attributed to the efficient immobilization of the peroxidase in the nanoclay, and the facilitation of electron transfer between the protein and the electrode surface due to the presence of the Pt nanoparticles and ionic liquid.

Modelling the Interaction of Catecholamines with the α1A Adrenoceptor Towards a Ligand-induced Receptor Structure

NASA Astrophysics Data System (ADS)

Kinsella, Gemma K.; Rozas, Isabel; Watson, Graeme W.

2005-06-01

Adrenoceptors are members of the important G protein coupled receptor family for which the detailed mechanism of activation remains unclear. In this study, we have combined docking and molecular dynamics simulations to model the ligand induced effect on an homology derived human α1A adrenoceptor. Analysis of agonist/α1A adrenoceptor complex interactions focused on the role of the charged amine group, the aromatic ring, the N-methyl group of adrenaline, the beta hydroxyl group and the catechol meta and para hydroxyl groups of the catecholamines. The most critical interactions for the binding of the agonists are consistent with many earlier reports and our study suggests new residues possibly involved in the agonist-binding site, namely Thr-174 and Cys-176. We further observe a number of structural changes that occur upon agonist binding including a movement of TM-V away from TM-III and a change in the interactions of Asp-123 of the conserved DRY motif. This may cause Arg-124 to move out of the TM helical bundle and change the orientation of residues in IC-II and IC-III, allowing for increased affinity of coupling to the G-protein.

Prefrontal/accumbal catecholamine system processes high motivational salience

PubMed Central

Puglisi-Allegra, Stefano; Ventura, Rossella

2012-01-01

Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme. Highly motivational experiences promote highly persistent memories. Although this phenomenon is adaptive in normal conditions, experiences with extremely high levels of motivational salience can promote development of memories that can be re-experienced intrusively for long time resulting in maladaptive outcomes. Neural mechanisms mediating motivational salience attribution are, therefore, very important for individual and species survival and for well-being. However, these neural mechanisms could be implicated in attribution of abnormal motivational salience to different stimuli leading to maladaptive compulsive seeking or avoidance. We have offered the first evidence that prefrontal cortical norepinephrine (NE) transmission is a necessary condition for motivational salience attribution to highly salient stimuli, through modulation of dopamine (DA) in the nucleus accumbens (NAc), a brain area involved in all motivated behaviors. Moreover, we have shown that prefrontal-accumbal catecholamine (CA) system determines approach or avoidance responses to both reward- and aversion-related stimuli only when the salience of the unconditioned stimulus (UCS) is high enough to induce sustained CA activation, thus affirming that this system processes motivational salience attribution selectively to highly salient events. PMID:22754514

Atherosclerotic changes of vessels caused by restriction of movement

NASA Technical Reports Server (NTRS)

Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

1980-01-01

The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

Behavioral Response of Dolphins to Signals Simulating Mid-Frequency Sonar

DTIC Science & Technology

2010-09-30

for cortisol and aldosterone and inspected for parallelism to determine whether a prolonged stress response is triggered by the sound exposure event...radioimmunoassay to assess circulating levels of corticosteroid hormones (cortisol and aldosterone ) and catecholamines (epinephrine). Levels will be compared...collected from the bottlenose dolphins. All samples have been processed for cortisol, aldosterone , and epinephrine. Assay kits have been validated for the

B-Type Natriuretic Peptide Reactivity to Mental Stress and Exercise: Role of Obesity and Hemodynamics

DTIC Science & Technology

2009-08-25

both of which increase SV and CO (Figure 16). Specifically, circulating catecholamines decrease venous compliance and increase central venous pressure...t Inotropy t Central Venous Pressure , t Preload / t SV&CO 104 References 1. The Criteria Committee of the New York Heart Association...Science Degrees -Public Health Masters Degrees -Military Medical History -Public Health -Tropical Medicine & Hygiene Graduate Education Office

Evaluation of the effects of zilpateral hydrochloride supplementation on catecholamine response and other blood metabolites following a combined corticotropin releasing hormone and vasopressin challenge

USDA-ARS?s Scientific Manuscript database

Supplementation of zilpaterol hydrochloride (ZH; Zilmax®) to cattle has been implicated as having a negative impact on the well-being of cattle. However, there is no data to support or refute these claims. This study was designed to determine if differences exist in the serum metabolic profile and m...

[Ventricular fibrillation following deodorant spray inhalation].

PubMed

Girard, F; Le Tacon, S; Maria, M; Pierrard, O; Monin, P

2008-01-01

We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

USSR Report, Life Sciences, Biomedical and Behavioral Sciences

DTIC Science & Technology

1987-01-20

Varnek, P. D. Brezhestovskiy; DOKLADY AKADEMII NAUK SSSR, No 6, Aug 86) 13 Effects of Selenomethionine on Proton Magnetic Relaxation in Hepatic ...Virus Expressing Surface Antigen of B Hepatitis Virus and Thymidinekinase of Herpes Simplex Virus (A. D. Altshteyn, 0. G. Andzhaparidze, et al...Influence of Dimetpramide and Metoclopramide on Catecholamine Turnover Rates in Rat Brain Subcortical-Brainstem Structures (V. I. Legeza, M. F. Kamynina

[Individual physical performance capacity with physiological and biochemical indicators of stress].

PubMed

Bergert, K D; Nestler, K; Böttger, H; Schettler, R

1989-09-01

22 health male subjects were exposed by a combination of physical exercises and heat. Strain related physiological and biochemical parameters were measured. Different individual reactions were obtained under controlled conditions. In dependence on the individual performance an increased mobilisation of lactat, free fatty acids and catecholamines were found. The determination of aerob physical performance can be applied for the evaluation of working capacity.

Chronic lithium treatment up-regulates cell surface Na(V)1.7 sodium channels via inhibition of glycogen synthase kinase-3 in adrenal chromaffin cells: enhancement of Na(+) influx, Ca(2+) influx and catecholamine secretion after lithium withdrawal.

PubMed

Yanagita, Toshihiko; Maruta, Toyoaki; Nemoto, Takayuki; Uezono, Yasuhito; Matsuo, Kiyotaka; Satoh, Shinya; Yoshikawa, Norie; Kanai, Tasuku; Kobayashi, Hideyuki; Wada, Akihiko

2009-09-01

In cultured bovine adrenal chromaffin cells expressing Na(V)1.7 isoform of voltage-dependent Na(+) channels, we have previously reported that lithium chloride (LiCl) inhibits function of Na(+) channels independent of glycogen synthase kinase-3 (GSK-3) (Yanagita et al., 2007). Here, we further examined the effects of chronic lithium treatment on Na(+) channels. LiCl treatment (1-30 mM, > or = 12 h) increased cell surface [(3)H]saxitoxin ([(3)H]STX) binding by approximately 32% without altering the affinity of [(3)H]STX binding. This increase was prevented by cycloheximide and actinomycin D. SB216763 and SB415286 (GSK-3 inhibitors) also increased cell surface [(3)H]STX binding by approximately 31%. Simultaneous treatment with LiCl and SB216763 or SB415286 did not produce an increased effect on [(3)H]STX binding compared with either treatment alone. LiCl increased Na(+) channel alpha-subunit mRNA level by 32% at 24 h. LiCl accelerated alpha-subunit gene transcription by 35% without altering alpha-subunit mRNA stability. In LiCl-treated cells, LiCl inhibited veratridine-induced (22)Na(+) influx as in untreated cells. However, washout of LiCl after chronic treatment enhanced veratridine-induced (22)Na(+) influx, (45)Ca(2+) influx and catecholamine secretion by approximately 30%. Washout of LiCl after 24 h treatment shifted concentration-response curve of veratridine upon (22)Na(+) influx upward, without altering its EC(50) value. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced (22)Na(+) influx by two-fold in untreated and LiCl-treated cells. Whole-cell patch-clamp analysis indicated that I-V curve and steady-state inactivation/activation curves were comparable between untreated and LiCl-treated cells. Thus, GSK-3 inhibition by LiCl up-regulated cell surface Na(V)1.7 via acceleration of alpha-subunit gene transcription, enhancing veratridine-induced Na(+) influx, Ca(2+) influx and catecholamine secretion.

On-line preconcentration of fluorescent derivatives of catecholamines in cerebrospinal fluid using flow-gated capillary electrophoresis.

PubMed

Zhang, Qiyang; Gong, Maojun

2016-06-10

Flow-gated capillary electrophoresis (CE) coupled with microdialysis has become an important tool for in vivo bioanalytical measurements because it is capable of performing rapid and efficient separations of complex biological mixtures thus enabling high temporal resolution in chemical monitoring. However, the limit of detection (LOD) is often limited to a micro- or nano-molar range while many important target analytes have picomolar or sub-nanomolar levels in brain and other tissues. To enhance the capability of flow-gated CE for catecholamine detection, a novel and simple on-line sample preconcentration method was developed exclusively for fluorescent derivatives of catecholamines that were fluorogenically derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide. The effective preconcentration coupled with the sensitive laser-induced fluorescence (LIF) detection lowered the LOD down to 20pM for norepinephrine (NE) and 50pM for dopamine (DA) at 3-fold of S/N ratio, and the signal enhancement was estimated to be over 100-fold relative to normal injection when standard analytes were dissolved in artificial cerebrospinal fluid (aCSF). The basic focusing principle is novel since the sample plug contains borate while the background electrolyte (BGE) is void of borate. This strategy took advantage of the complexation between diols and borate, through which one negative charge was added to the complex entity. The sample derivatization mixture was electrokinetically injected into a capillary via the flow-gated injection, and then NE and DA derivatives were selectively focused to a narrow zone by the reversible complexation. Separation of NE and DA derivatives was executed by incoming surfactants of cholate and deoxycholate mixed in the front BGE plug. This on-line preconcentration method was finally applied to the detection of DA in rat cerebrospinal fluid (CSF) via microdialysis and on-line derivatization. It is anticipated that the method would be valuable for in vivo monitoring of DA and NE in various brain regions of live animals on flow-gated CE or microchip platforms. Published by Elsevier B.V.

Mechanisms of lower body negative pressure-induced syncope

NASA Astrophysics Data System (ADS)

Davrath, Linda Ruble

Although extensively investigated, the mechanisms of post-spaceflight orthostatic intolerance have not been elucidated. The working hypothesis was that a markedly reduced left ventricular end-systolic volume (LVESV) would be achieved during progressive, presyncopal-limited LBNP and would cause bradycardia and a fall in blood pressure, thus triggering syncope. Eight healthy men, age 25.1 ± 1.3 years, volunteered for the study. Subjects were exposed to graded levels of LBNP on two separate occasions. Changes in left ventricular end-diastolic volume and LVESV were measured, using two-dimensional echocardiography, at each stage of LBNP from rest to presyncope. Plasma venous blood samples were withdrawn at the end of each stage of the LBNP protocol for the measurement of plasma venous catecholamines and plasma renin activity (PRA). Catecholamines were analyzed by HPLC with electro-chemical detection, and PRA was determined by radioimmunoassay. All subjects reached presyncope during the LBNP. LVESV decreased by 28% at presyncope with no evidence of ventricular cavity obliteration. Norepinephrine (NE) increased by 44% from rest to presyncope, but no epinephrine surge was detected (35% increase from rest to presyncope). These data indicate that it is possible to initiate syncope with only a 28% decrease in LVESV, and that sympatho-inhibition and bradycardia are not required elements for syncope to occur. To investigate the effect of moderate sodium restriction on cardiovascular hemodynamics and orthostatic tolerance, presyncopal LBNP testing was performed. Urinary sodium excretion was significantly higher on the normal-sodium diet when compared with the sodium-restricted diet, but urinary potassium was not different. Cumulative stress index (655 ± 460 on normal-sodium diet vs. 639 ± 388 on sodium-restricted diet) scores were not different. Cardiac volumes, blood pressure and total peripheral resistance were not different at any stage of the LBNP between the diets, nor were plasma catecholamine levels. Heart rate was significantly higher at presyncope on the sodium-restricted diet. Plasma renin activity was significantly higher during sodium restriction at rest, and during all stages of LBNP. Moderate dietary sodium restriction was not accompanied by apparent plasma volume reduction (hematocrit, body weight change), and did not appear to be detrimental to orthostatic function.

Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress.

PubMed

Hanke, M L; Powell, N D; Stiner, L M; Bailey, M T; Sheridan, J F

2012-10-01

During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation. Copyright © 2012 Elsevier Inc. All rights reserved.

A Bibliography of Shift Work Research: 1950-1982

DTIC Science & Technology

1983-09-01

Opladen: Westdeutscher Verlag, pp. 103-112, 1975. :%i 630. Kojima, A., and Y. Niiyama: Diurnal Variations of 17- Ketogenic Steroid and Catecholamine...Experimental Food and Drinking Diet . Studia Laboris et Salutis, 11:42-45, 1972. 813. Miura, K.: Industrial Fatigue Survey on Three Shift Workers, Part 1... Ketogenic Steriod Excretion and the Adaptation to Changes of the Activity-Sleep Routine. Journal of Endocrinology, 22:377-385, 1961. 1083. Shephard, R

People’s Republic of China Scientific Abstracts, Number 167.

DTIC Science & Technology

1977-04-28

Station, Kwang-si Huan-chiang County TITLE: "Treatment of Uterine Prolapse with Urena Lobata and Eucommia Ulmoides Decoction and Acupuncture" SOURCE... uterine prolapse were treated with Urena lobata and eucommia ulmoides decoction and acupuncture. The decoction was taken twice daily. Acupuncture...rabbits and dogs it was shown that both atropine and scopo- lamine were able to counteract the arrhythmia caused by catecholamines, but could not

Catecholamine Enhancement and Visual Cortex Plasticity in Developing Kittens.

DTIC Science & Technology

1982-03-01

ohm impedance tungsten-in-glass micro- electrode ( Levick , 1970). The output voltage changes were transmitted to an audio monitor through selectable...osmotic minipump. B . Illustration of injection method to fill iminpump and the assembled system. Figure 2 - Ocular dominance histograms of each...suppression with 6-hydroxydopamine. J. Neurophysiol. 45(2)t 254-266. Levick , W.R. (1972) Another tungsten microelectrode. Ked. and Fiol. Eng. 101 510-515

Catecholamines in Post-Traumatic Stress Disorder

DTIC Science & Technology

2012-07-01

could lead to memories that are too strong, contributing to the recurrent, intrusive retrieval of the traumatic events that occurs in PTSD. As a...emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder...signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep. J Neurophysiol 92:2071–2082. Ouyang M, Zhang L, Zhu

An unusual case of hematemesis and epistaxis caused by a pheochromocytoma.

PubMed

Ugur, Kader; Girgin, Mustafa; Bahcecioglu, İbrahim Halil; Artas, Hakan; Selcuk Simsek, Fikri; Aydin, Suleyman

2018-01-01

Pheochromocytoma is a rare catecholamine-secreting neoplasm that is the cause of hypertension in <0.2% of patients with hypertension. We encountered an unusual case of pheochromocytoma involving hematemesis and epistaxis episodes with accompanying hypertensive attacks. Venous ectasia was detected in the esophagus. Abdominal magnetic resonance imaging revealed an adenoma in the left adrenal region. The present case illustrates that pheochromocytoma can mimic different clinical conditions.

Investigation of the Physiological Responses of Belugas to Stressors to Aid in Assessing the Impact of Environmental and Anthropogenic Challenges on Health

DTIC Science & Technology

2013-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. FINAL REPORT Investigation of the Physiological Responses...The overall top level goal of this effort is to investigate the physiological i.e. neuroimmunoendocrinological responses of beluga whales to...adrenocorticotropin hormone, aldosterone , catecholamines) in different matrices (blood, saliva, blow, feces) in conjunction with immune function

Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

DTIC Science & Technology

2013-09-30

cortisol and aldosterone impacted glucose, lactate, NEFA , BUN and electrolyte levels. These data provide novel information on the physiological and...massey.ac.nz Award Number: N000141110434 LONG-TERM GOALS Physiological indicators of stress in wild marine mammals, the interrelationships...glucocorticoid hormones (GC), aldosterone (A), thyroid hormones (TH), and catecholamines within a free-ranging northern elephant seal population and its

Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

DTIC Science & Technology

2014-09-30

cortisol and aldosterone impacted glucose, lactate, NEFA , BUN and electrolyte levels. These data provide novel information on the physiological and...massey.ac.nz Award Number: N000141110434 LONG-TERM GOALS Physiological indicators of stress in wild marine mammals, the interrelationships between...hormones (GC), aldosterone (A), thyroid hormones (TH), and catecholamines within a free-ranging northern elephant seal population and its dependence