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Sample records for reserpine

  1. Enantioselective Total Synthesis of (+)-Reserpine

    PubMed Central

    Rajapaksa, Naomi S.; McGowan, Meredeth A.; Rienzo, Matthew

    2013-01-01

    A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels–Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate. PMID:23331099

  2. Reserpine

    MedlinePlus

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  3. The anti-hypertensive drug reserpine induces neuronal cell death through inhibition of autophagic flux.

    PubMed

    Lee, Kang Il; Kim, Min Ju; Koh, Hyongjong; Lee, Jin I; Namkoong, Sim; Oh, Won Keun; Park, Junsoo

    2015-07-10

    Reserpine is a well-known medicine for the treatment of hypertension and schizophrenia, but its administration can induce Parkinson's disease (PD)-like symptoms in humans and animals. Reserpine inhibits the vesicular transporter of monoamines and depletes the brain of monoamines such as dopamine. However, the cellular function of reserpine is not fully understood. In this report, we present one possible mechanism by which reserpine may contribute to PD-like symptoms. Reserpine treatment induced the formation of enlarged autophagosomes by inhibiting the autophagic flux and led to accumulation of p62, an autophagy adapter molecule. In particular, reserpine treatment increased the level of α-synuclein protein and led to accumulation of α-synuclein in autophagosomes. Treatment with rapamycin enhanced the effect of reserpine by further increasing the level of α-synuclein and neuronal cell death. Drosophila raised on media containing reserpine showed loss of dopaminergic neurons. Furthermore, cotreatment with reserpine and rapamycin aggravated the loss of dopaminergic neurons. Our results suggest that reserpine contributes to the loss of dopaminergic neurons by interfering with autophagic flux. PMID:25976674

  4. Effects of methysergide on platelets incubated with reserpine

    PubMed Central

    Cumings, J. N.; Hilton, Barbara P.

    1971-01-01

    1. Platelets were incubated with methysergide and related compounds (2-bromo lysergic acid (BOL), ergotamine and methyl ergotamine) together with reserpine. 2. Methysergide inhibited the normal aggregation response of platelets to 5-hydroxytryptamine (5HT) but did not affect the reduction in the 5HT content caused by reserpine, or the uptake of 5HT by the platelets. 3. BOL, ergotamine and methyl ergotamine behaved similarly. Methysergide had greater anti5HT potency than BOL, and methyl ergotamine had greater potency than ergotamine. 4. The use of platelets as a model for synaptic preparations is discussed. 5. The role of 5HT receptor sites on the platelet membrane and the significance of the results for migraine patients treated with methysergide are discussed. PMID:5116036

  5. Adenosine signaling in reserpine-induced depression in rats.

    PubMed

    Minor, Thomas R; Hanff, Thomas C

    2015-06-01

    A single, 6 mg/kg intraperitoneal injection of reserpine increased floating time during forced swim testing 24h after administration in rats in five experiments. Although such behavioral depression traditionally is attributed to drug-induced depletion of brain monoamines, we examined the potential contribution of adenosine signaling, which is plausibly activated by reserpine treatment and contributes to behavioral depression in other paradigms. Whereas peripheral administration of the highly selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.5, 1.0, or 5.0mg/kg i.p.) 15 min before swim testing failed to improve performance in reserpine-treated rats, swim deficits were completely reversed by 7 mg/kg of the nonselective receptor antagonist caffeine. Performance deficits were also reversed by the nonselective A2 antagonist 3,7-dimethylxanthine (0, 0.5, 1.0mg/kg i.p.), and the highly selective A2A receptor antagonist (CSC: 8-(3 chlorostyral)caffeine) (0.01, 0.1, or 1.0mg/kg i.p.) in a dose-dependent manner. The highly selective A2B antagonist alloxazine had no beneficial effect on swim performance at any dose under study (0.1, 1.0, and 5.0mg/kg i.p.). PMID:25721738

  6. Evidence for a reserpine-affected mechanism of resistance to tetracycline in Neisseria gonorrhoeae.

    PubMed

    Ruiz, Joaquim; Ribera, Anna; Jurado, Angels; Marco, Francesc; Vila, Jordi

    2005-10-01

    The presence of a reserpine-affected mechanism of tetracycline resistance was investigated in 17 Neisseria gonorrhoeae clinical isolates. To establish this fact the MIC of tetracycline in the presence and absence of reserpine was determined, and, in addition, mechanisms of tetracycline resistance were analyzed by PCR. The results showed that reserpine affects the MIC of tetracycline at least 4-fold in all isolates, including those containing the tetM gene. An inhibitory effect of reserpine against the MtrCDE efflux system was ruled out by using strains either with an inactive or with an unrepressed MtrCDE system. The results suggest the presence of a constitutive system of resistance to tetracycline, by a possible efflux pump, which may be inhibited by reserpine. Further studies are required to determine the exact nature of the action of reserpine on the MIC of tetracycline. PMID:16309425

  7. Decreased synthesis of DNA in regenerating rat liver after the administration of reserpine

    PubMed Central

    Ćihák, A.; Vaptzarova, K.

    1973-01-01

    1. Reserpine given to rats before the enhanced synthesis of DNA begins 14h after partial hepatectomy markedly depresses thymidine uptake into DNA at 24 hours. 2. At this time decreased activity of liver thymidine kinase but unchanged thymidine 5′-nucleotidase were observed. 3. Reserpine has no effect on DNA synthesis when administered simultaneously with the labelled thymidine 2 h before killing. 4. With depressed DNA synthesis after reserpine administration there is no significant decrease of liver RNA synthesis. PMID:4793440

  8. 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

  9. Effect of reserpine on salivary gland radioiodine uptake in thyroid cancer

    SciTech Connect

    Levy, H.A.; Park, C.H.

    1987-04-01

    Nine patients with thyroid cancer were treated with reserpine in an attempt to reduce radiation exposure to the salivary glands from 100-150 mCi doses of I-131 therapy to thyroid remnants or metastases. Three control patients were not treated with reserpine but did receive 100-150 mCi of I-131. Parotid/background ratios of activity after radioablative doses of I-131 in patients not treated with reserpine were significantly higher than the patients treated with reserpine, and this was also true seven days after the radioablative dose. Combined therapy with reserpine, chewing gum, lemon candies, and hydration is suggested for the prevention of sialadenitis and xerostomia due to large doses of radioiodine.

  10. The metabolism of histamine in rat hypothalamus and cortex after reserpine treatment.

    PubMed

    Maldonado, Martin; Maeyama, Kazutaka

    2015-01-01

    The effect of reserpine on histamine (HA) and tele-methylhistamine (N(τ)-MHA) in hypothalamus and cortex of rats was analyzed and compared to catecholamines. IP injection of reserpine (5 mg/kg) confirmed the effectiveness of reserpine treatment on noradrenaline and dopamine levels. Our in-vitro experiment with synaptosomal/crude mitochondrial fraction from hypothalamus and cortex confirmed that while mono amine oxidase (MAO) is an efficient metabolic enzyme for catecholamines, HA is not significantly affected by its enzymatic action. HMT activity after reserpine, pargyline and L-histidine treatment showed no differences compared to the control values. However HDC was significantly increased in both hypothalamus and cortex. In this study, Ws/Ws rats with deficiency of mast cells were used to clarify aspects of HA metabolism in HAergic neurons by eliminating the contribution of mast cells. The irreversible MAO-B inhibitor Pargyline (65 mg/kg) failed to accumulate N(τ)-MHA in the hypothalamus. However, when animals treated with reserpine and pargyline/reserpine were compared, the last group showed higher N(τ)-MHA values (p < 0.01). Moreover, the precursor of HA, L-histidine (1 g/kg), produced an increase of HA in the hypothalamus to 166% and the cortex to 348%. In conclusion, our results suggest that the effect of reserpine on the HA pools in the brain might be different. The neuronal HA pools are more resistant to reserpine as compared to those of catecholamine. Moreover, the HAergic pool appears to be more resistant to depletion than mast cells' pool, and thus HDC/HMT activity and its localization may play a key role in the understanding of HA metabolism in brain after reserpine treatment. PMID:25936509

  11. Reserpine withdrawal psychosis: the possible role of denervation supersensitivity of receptors.

    PubMed

    Kent, T A; Wilber, R D

    1982-08-01

    A case is reported in which abrupt cessation of long term reserpine therapy for hypertension was followed by hallucinations and mania. Reserpine is thought to induce a denervation sensitivity to dopamine in the basal ganglia and chemotactic trigger zone in man and to catecholaminergic agents in the basal ganglia and mesolimbic system in animals. Conceivably, a parallel supersensitivity in the mesolimbic area could have occurred in this patient and accounted for the psychiatric symptoms. This supersensitivity and the possibility that it may, like tardive dyskinesia, be persistent should be considered when reserpine or similar drugs are used for prolonged periods. PMID:7097268

  12. Expression cloning of a reserpine-sensitive vesicular monoamine transporter.

    PubMed Central

    Erickson, J D; Eiden, L E; Hoffman, B J

    1992-01-01

    A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules. Images PMID:1438304

  13. Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats.

    PubMed

    Nade, V S; Dwivedi, Subhash; Kawale, L A; Upasani, C D; Yadav, A V

    2009-07-01

    Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg/kg) was studied on reserpine-induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg/kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg/kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine-induced orofacial dyskinesia and oxidative stress. PMID:19761039

  14. Echinocystic acid reduces reserpine-induced pain/depression dyad in mice.

    PubMed

    Li, Shuo; Han, Jing; Wang, Dong-Sheng; Feng, Bin; Deng, Ya-Ting; Wang, Xin-Shang; Yang, Qi; Zhao, Ming-Gao

    2016-04-01

    Chronic pain has consistently been correlated with depression. Echinocystic acid (EA), a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries, exhibits anti-inflammatory and analgesic activities. However, little is known the effects of EA on the depression. In present study, we investigated the anti-depression activities in the mouse model of reserpine-induced pain-depression dyad. Reserpine (1 mg/kg subcutaneously daily for 3 days) caused significant depression-like behaviors and pain sensation. Subsequent treatment of EA (5 mg/kg intragastrically daily for 5 days) attenuated the reserpine-induced pain/depression dyad as shown by the increase of pain threshold and the behaviors in forced swimming test, tail suspension test, and open field test. Furthermore, treatment of EA reversed the decrease of biogenic amines (norepinephrine, dopamine, and serotonin) in the brain region of hippocampus, a structure involved in the formation of emotional disorders. Levels of serotonin receptor 5-HT1A were decreased and levels of 5-HT2A were increased in the reserpine-injected mice. Treatment of EA could restore the alterations of serotonin receptors. At the same time, the increase in GluN2B-containing NMDA receptors, p-GluA1-Ser831, PSD-95 and CaMKII were integrated with the increase in caspase-3 and iNOS levels in the hippocampus of the reserpine-injected mice. EA significantly reversed the changes of above proteins. However, EA did not affect the levels of GluN2A-containing NMDA receptors and the total levels of GluA1 and p-GluA1-Ser845. Our study provides strong evidence that EA attenuates reserpine-induced pain/depression dyad partially through regulating the biogenic amines levels and GluN2B receptors in the hippocampus. PMID:26729203

  15. Valeriana officinalis ameliorates vacuous chewing movements induced by reserpine in rats.

    PubMed

    Pereira, Romaiana Picada; Fachinetto, Roselei; de Souza Prestes, Alessandro; Wagner, Caroline; Sudati, Jéssie Haigert; Boligon, Aline Augusti; Athayde, Margareth Linde; Morsch, Vera Maria; Rocha, João Batista Teixeira

    2011-11-01

    Oral movements are associated with important neuropathologies as Parkinson's disease and tardive dyskinesia. However, until this time, there has been no known efficacious treatment, without side effects, for these disorders. Thus, the aim of the present study was to investigate the possible preventive effects of V. officinalis, a phytotherapic that has GABAergic and antioxidant properties, in vacuous chewing movements (VCMs) induced by reserpine in rats. Adult male rats were treated with reserpine (1 mg/kg, s.c.) and/or with V. officinalis (in the drinking water, starting 15 days before the administration of the reserpine). VCMs, locomotor activity and oxidative stress measurements were evaluated. Furthermore, we carried out the identification of valeric acid and gallic acid by HPLC in the V. officinalis tincture. Our findings demonstrated that reserpine caused a marked increase on VCMs and the co-treatment with V. officinalis was able to reduce the intensity of VCM. Reserpine did not induce oxidative stress in cerebral structures (cortex, hippocampus, striatum and substantia nigra). However, a significant positive correlation between DCF-oxidation (an estimation of oxidative stress) in the cortex and VCMs (p < 0.05) was observed. Moreover, a negative correlation between Na(+)K(+)-ATPase activity in substantia nigra and the number of VCMs was observed (p < 0.05). In conclusion, V. officinalis had behavioral protective effect against reserpine-induced VCMs in rats; however, the exact mechanisms that contributed to this effect have not been completely understood. PMID:21476069

  16. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    SciTech Connect

    Neisewander, J.L.; Lucki, I.; McGonigle, P. )

    1991-05-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with ({sup 3}H)SCH-23390 and D2 receptors labeled with ({sup 3}H)spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia.

  17. Effects of Reserpine on Reproduction and Serotonin Immunoreactivity in the Stable Fly Stomoxys Calcitrans (L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biogenic amines are known to play critical roles in key insect behaviors such as feeding and reproduction. This study documents the effects of reserpine on mating and egg-laying behaviors of the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), which is one of the most economically significa...

  18. The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats.

    PubMed

    Gao, Zhen-Yong; Yang, Ping; Huang, Qing-Jun; Xu, Hai-Yun

    2016-02-12

    Clinical studies have demonstrated that a single dose of ketamine produces complete remission within 24h in some depression patients. The ability of ketamine to produce fast-acting antidepressant-like effects in animal models depends on rapid synthesis of brain-derived neurotrophic factor (BDNF). Here we examined effects of a single dose dizocilpine, a non-competitive NMDA receptor antagonist, on the behavioral and neurobiological changes in rats treated with a single high dose reserpine, which is a monoamine re-uptake blocker and depletes monoamines in the brain with the outcome of depression-like symptoms in animals. A single high dose reserpine (4.0mg/kg) was given to rats intraperitoneally. Forty-eight hours later, the rats showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swim test. Meanwhile, the treatment decreased BDNF levels and neurogenesis in the hippocampus. Pretreatment of a single dose dizocilpine (0.30mg/kg), however, prevented all the reserpine-induced changes, except for GluN1 subunit. These results are suggestive of the involvement of neurogenesis and BDNF in the rapid-acting antidepressant-like behavioral effects of the NMDA receptor antagonists in the reserpinized rats. PMID:26779676

  19. Kinetics and Thermodynamics of Reserpine Adsorption onto Strong Acidic Cationic Exchange Fiber

    PubMed Central

    Guo, Zhanjing; Liu, Xiongmin; Huang, Hongmiao

    2015-01-01

    The kinetics and thermodynamics of the adsorption process of reserpine adsorbed onto the strong acidic cationic exchange fiber (SACEF) were studied by batch adsorption experiments. The adsorption capacity strongly depended on pH values, and the optimum reserpine adsorption onto the SACEF occurred at pH = 5 of reserpine solution. With the increase of temperature and initial concentration, the adsorption capacity increased. The equilibrium was attained within 20 mins. The adsorption process could be better described by the pseudo-second-order model and the Freundlich isotherm model. The calculated activation energy Ea was 4.35 kJ/mol. And the thermodynamic parameters were: 4.97<ΔH<7.44 kJ/mol, -15.29<ΔG<-11.87 kJ/mol and 41.97<ΔS<47.35 J/mol·K. The thermodynamic parameters demonstrated that the adsorption was an endothermic, spontaneous and feasible process of physisorption within the temperature range between 283 K and 323 K and the initial concentration range between 100 mg/L and 300 mg/L. All the results showed that the SACEF had a good adsorption performance for the adsorption of reserpine from alcoholic solution. PMID:26422265

  20. Effect of reserpine on the histochemical and biochemical properties of rat intestinal mucin

    SciTech Connect

    Forstner, J.; Roomi, N.; Khorasani, R.; Kuhns, W.; Forstner, G. )

    1991-04-01

    Biochemical and histochemical parameters of intestinal mucins were examined in control and reserpine-treated rats. An assay for intestinal mucin sulfotransferase was developed and the activity shown to increase 3.4 times over control levels in rats given intraperitonal reserpine (0.5 mg/kg body wt) daily for 7 days. Histochemical staining of intestinal sections revealed an increase in sulfomucins in goblet cells of reserpine-treated rats. The effects were prominent as early as 1 day following injection, particularly in the distal third of the small intestine, and during the next 6 days these changes spread progressively to the middle and proximal thirds. After 3 days of treatment mucins were purified from each intestinal segment and compared to control mucins with respect to composition and (35S)NaSO{sub 4} incorporation. Although individual amino acid and carbohydrate molar ratios were unchanged, the total carbohydrate and sulfate content of mucins in treated animals was elevated (two to three times above control) in the middle and distal thirds of the intestine. In vivo ({sup 35}S)SO{sub 4} incorporation into these mucins was also proportionaltely elevated, and was targetted to O-linked oligosaccharide side chains. These findings are consistent with an action of reserpine causing an increased production of mucin which is enriched in glycoprotein components bearing sulfated oligosaccharide chains. The relevance of these findings to the production of hypersulfated and hyperglycosylated mucins in cystic fibrosis is discussed.

  1. Mammogenesis and induced lactation with or without reserpine in nulliparous dairy goats.

    PubMed

    Salama, A A K; Caja, G; Albanell, E; Carné, S; Casals, R; Such, X

    2007-08-01

    Nulliparous goats were used to evaluate the effects of a standard protocol for inducing lactation with or without using a prolactin-releasing agent (reserpine). Estrus was synchronized and goats were submitted to daily s.c. injections of estradiol-17beta and progesterone (0.5 and 1.25 mg/kg of body weight, respectively) for 7 d. The goats were divided into 2 groups and injected i.m. with 1 mg/d of reserpine (n = 7) or the vehicle (n = 7) on d 12, 14, 16, 18, and 20. Lactation was initiated by i.m. injections of dexamethasone (10 mg/d) from d 18 to 20. Goats were machine milked once daily from d 21 to 120, at which time they were mated with herd sires. Milk was measured and sampled daily during wk 1 of lactation and weekly thereafter. Udder traits were measured in all goats at d -2 (before the induction treatment) and on d 35 and 100 (during lactation). Goats initiated lactation on d 21 (100%) and milk yield increased thereafter. The milk yield of control and reserpine-treated goats increased as lactation advanced, peaking at wk 10 of lactation, when reserpine-treated goats yielded 1,079 +/- 89 mL/d of milk compared with 850 +/- 96 mL/d for control goats. Yet milk yield at the peak was only 55% of the peak milk yield observed in contemporary primiparous goats. The composition of initial milk (d 21) was different from that expected for colostrum. Milk composition stabilized after d 3 of lactation. There were no differences among groups for milk fat, protein, casein, or whey protein, but milk from control goats contained greater nonprotein nitrogen than that from reserpine-treated goats (0.48 +/- 0.02 vs. 0.41 +/- 0.02%). Teat length increased from 24.7 +/- 1.1 to 34.5 +/- 2.4 mm in control goats during mammogenesis (d -2 to 35), but stabilized in reserpine goats (25.2 +/- 2.2 mm). The distance between teats (11.5 +/- 0.4 cm), and the volume (922 +/- 63 mL) and depth (15.6 +/- 0.60 cm) of the udder increased similarly in both groups during mammogenesis and lactation

  2. The usefulness of olfactory fear conditioning for the study of early emotional and cognitive impairment in reserpine model.

    PubMed

    Souza, Rimenez R; França, Sanmara L; Bessa, Marília M; Takahashi, Reinaldo N

    2013-11-01

    Due to the ability for depleting neuronal storages of monoamines, the reserpine model is a suitable approach for the investigation of the neurobiology of neurodegenerative diseases. However, the behavioral effects of low doses of reserpine are not always detected by classic animal tests of cognition, emotion, and sensory ability. In this study, the effects of reserpine (0.5-1.0mg/kg) were evaluated in olfactory fear conditioning, inhibitory avoidance, open-field, elevated plus-maze, and olfactory discrimination. Possible protective effects were also investigated. We found that single administration of reserpine impaired the acquisition of olfactory fear conditioning (in both doses) as well as olfactory discrimination (in the higher dose), while no effects were seen in all other tests. Additionally, we demonstrated that prior exposure to environmental enrichment prevented effects of reserpine in animals tested in olfactory fear conditioning. Altogether, these findings suggest that a combined cognitive, emotional and sensory-dependent task would be more sensitive to the effects of the reserpine model. In addition, the present data support the environmental enrichment as an useful approach for the study of resilience mechanisms in neurodegenerative processes. PMID:23978602

  3. Behavioral effects of bidirectional modulation of brain monoamines by reserpine and d-amphetamine in zebrafish

    PubMed Central

    Kyzar, Evan; Stewart, Adam Michael; Landsman, Samuel; Collins, Christopher; Gebhardt, Michael; Robinson, Kyle; Kalueff, Allan V.

    2013-01-01

    Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines’ levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism for drug screening and translational neuroscience research. Here, we have examined the acute and long-term effects of reserpine and d-amphetamine on zebrafish behavior in the novel tank test. Overall, d-amphetamine (5 and 10 mg/L) evokes anxiogenic-like effects in zebrafish acutely, but not 7 days later. In contrast, reserpine (20 and 40 mg/L) did not evoke overt acute behavioral effects, but markedly reduced activity 7 days later, resembling motor retardation observed in depression and/or Parkinson’s disease. Three-dimensional ‘temporal’ (X, Y, Time) reconstructions of zebrafish locomotion further supports these findings, confirming the utility of 3D-based video-tracking analyses in zebrafish models of drug action. Our results show that zebrafish are highly sensitive to drugs bi-directionally modulating brain monoamines, generally paralleling rodent and clinical findings. Collectively, this emphasizes the potential of zebrafish tests to model complex brain disorders associated with monoamine dysregulation. PMID:23827499

  4. Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long-Standing Model.

    PubMed

    Leão, Anderson H F F; Sarmento-Silva, Aldair J; Santos, José R; Ribeiro, Alessandra M; Silva, Regina H

    2015-07-01

    The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L-DOPA and dopamine agonists. Nevertheless, with the introduction of toxin-induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD. PMID:25726735

  5. Effects of denervation and reserpine on nexuses in the rat vas deferens.

    PubMed

    Westfall, D P; Millecchia, L L; Lee, T J; Corey, S P; Smith, D J; Fleming, W W

    1977-01-21

    Permanganate-fixed vasa deferentia from rats were examined for the presence of nexal-like contacts by electron microscopy. There was a significantly greater incidence of nexuses (2X) in chronically denervated tissues (5-7 days) but not in tissues from reserpine-pretreated animals (1.0 mg/kg/day for 5-7 days). The results suggest that an increase in nexal regions may not be a general feature of postjunctional supersensitivity but rather may contribute to other denervation-induced changes in contractile response. PMID:832678

  6. Accumbal α-adrenoceptors, but not β-adrenoceptors, regulate behaviour that is mediated by reserpine-sensitive storage vesicles.

    PubMed

    Verheij, Michel M M; Saigusa, Tadashi; Koshikawa, Noriaki; Cools, Alexander R

    2015-02-01

    It has previously been demonstrated that mesolimbic α-adrenoceptors, but not β-adrenoceptors, control the release of dopamine that is derived from reserpine-sensitive storage vesicles. The aim of the present study was to investigate whether these storage vesicles also regulate α-adrenoceptor-mediated or β-adrenoceptor-mediated changes in behaviour. Accordingly, rats were pretreated with reserpine before the α-adrenoceptor antagonist phentolamine or the β-adrenoceptor agonist isoproterenol was locally applied to the nucleus accumbens. Both phentolamine and isoproterenol increased the duration of walking, rearing and grooming and decreased the duration of sitting. Reserpine counteracted the behavioural response elicited by phentolamine but not by isoproterenol. The results of the present study demonstrate that mesolimbic α-adrenoceptors, but not β-adrenoceptors, regulate behaviour that is mediated by reserpine-sensitive storage pools. It is hypothesized that the observed α-adrenoceptor-mediated increase in locomotor activity is due to the α-adrenoceptor-mediated increase in the release of accumbal intravesicular dopamine. Our finding that α-adrenoceptors inhibit, whereas β-adrenoceptors stimulate, locomotor activity may help explain why noradrenaline or environmental stressors have previously been found to have opposing effects on the regulation of behaviour. PMID:25325287

  7. Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors.

    PubMed

    Cunha, Andréia S; Matheus, Filipe C; Moretti, Morgana; Sampaio, Tuane B; Poli, Anicleto; Santos, Danúbia B; Colle, Dirleise; Cunha, Mauricio P; Blum-Silva, Carlos H; Sandjo, Louis P; Reginatto, Flávio H; Rodrigues, Ana Lúcia S; Farina, Marcelo; Prediger, Rui D

    2016-10-01

    Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.p.) administration of different agmatine doses (10, 30 or 100mg/kg) against the orofacial dyskinesia induced by reserpine (1mg/kg,s.c.) in mice by measuring the vacuous chewing movements and tongue protusion frequencies, and the duration of facial twitching. The results showed an orofacial antidyskinetic effect of agmatine (30mg/kg, i.p.) or the combined administration of sub-effective doses of agmatine (10mg/kg, i.p.) with the NMDA receptor antagonists amantadine (1mg/kg, i.p.) and MK801 (0.01mg/kg, i.p.) or the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI; 0.1mg/kg, i.p.). Reserpine-treated mice displayed locomotor activity deficits in the open field and agmatine had no effect on this response. Reserpine increased nitrite and nitrate levels in cerebral cortex, but agmatine did not reverse it. Remarkably, agmatine reversed the decrease of dopamine and non-protein thiols (NPSH) levels caused by reserpine in the striatum. However, no changes were observed in striatal immunocontent of proteins related to the dopaminergic system including tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter type 2, pDARPP-32[Thr75], dopamine D1 and D2 receptors. These results indicate that the blockade of NO pathway, NMDAR and oxidative stress are possible mechanisms associated with the protective effects of agmatine against the orofacial dyskinesia induced by reserpine in mice. PMID

  8. Evaluation of anti-colitic effect of fluvoxamine against acetic acid-induced colitis in normal and reserpinized depressed rats.

    PubMed

    Minaiyan, Mohsen; Hajhashemi, Valiollah; Rabbani, Mohammad; Fattahian, Ehsan; Mahzouni, Parvin

    2015-01-01

    High prevalence of psychological comorbidities such as depression and anxiety in patients with inflammatory bowel disease (IBD) supports the premise that adding an anti-depressant drug with known anti-inflammatory effect to the medical treatment have beneficial effect in the course of the underlying disease. Colitis was induced by intracolonic instillation of 2 ml of 4% v/v acetic acid solution in rats. Anti-colitic effect of fluvoxamine was evaluated in two categories: A: normal rats, B: reserpinized (6 mg/kg, i.p.) depressed rats. In group A, fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after induction of colitis and in group B: reserpine (6 mg/kg, i.p.) was administered 1 h prior to colitis induction and then fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after colitis induction. Dexamethasone (1 mg/kg) was used as reference drug. All the treatments continued daily for five days. The effect was assessed on the basis of macroscopic score, biochemical (myeloperoxidase) changes and histopathological studies. Results showed that fluvoxamine (2.5 and 5 mg/kg) and dexamethasone treatment markedly reduced disease severity in both reserpinized and non-reserpinized rats as indicated by reduction in macroscopic and microscopic colonic damages while reserpine adversely exacerbated the colitis damage. Myeloperoxidase activity which was increased following colitis induction was also decreased. The findings of this study elucidate the anti-colitic and anti-inflammatory properties of fluvoxamine and so introduced it as a good candidate to treat depressive symptoms in people comorbid to IBD. PMID:25460023

  9. Simultaneous Estimation of Hydrochlorothiazide, Hydralazine Hydrochloride, and Reserpine Using PCA, NAS, and NAS-PCA

    PubMed Central

    Sharma, Chetan; Badyal, Pragya Nand; Rawal, Ravindra K.

    2015-01-01

    In this study, new and feasible UV-visible spectrophotometric and multivariate spectrophotometric methods were described for the simultaneous determination of hydrochlorothiazide (HCTZ), hydralazine hydrochloride (H.HCl), and reserpine (RES) in combined pharmaceutical tablets. Methanol was used as a solvent for analysis and the whole UV region was scanned from 200–400 nm. The resolution was obtained by using multivariate methods such as the net analyte signal method (NAS), principal component analysis (PCA), and net analyte signal-principal component analysis (NAS-PCA) applied to the UV spectra of the mixture. The results obtained from all of the three methods were compared. NAS-PCA showed a lot of resolved data as compared to NAS and PCA. Thus, the NAS-PCA technique is a combination of NAS and PCA methods which is advantageous to obtain the information from overlapping results. PMID:26839841

  10. Influence of reserpine-induced depletion of noradrenaline on the negative feed-back mechanism for transmitter release during nerve stimulation

    PubMed Central

    Enero, María A.; Langer, S. Z.

    1973-01-01

    1. The effects of depletion of endogenous noradrenaline by reserpine-pretreatment on [3H]-noradrenaline overflow elicited by nerve stimulation were determined in the isolated nerve-muscle preparation of the cat's nictitating membrane. 2. Reserpine pretreatment (0·3 mg/kg, s.c., 4 days prior to the experiment) reduced the noradrenaline levels in the smooth muscle of the nictitating membrane to about 10% of the control values while granular retention of [3H]-noradrenaline had recovered to nearly 40% of the controls. 3. In the reserpine-pretreated tissue the fraction release per shock induced by nerve stimulation was 2·2-fold higher than the value obtained in the untreated tissues. This effect was correlated with the degree of depletion of the noradrenaline stores rather than with the decrease in the response of the effector organ. 4. Phenoxybenzamine, 2·9 μM reduced the responses to nerve stimulation to the same extent in control and in reserpine-pretreated tissues. Yet, this concentration of phenoxybenzamine increased by 13-fold the overflow of the labelled transmitter in the controls and only by 3-fold in reserpine-pretreated tissues. 5. The decrease in effectiveness of phenoxybenzamine in enhancing transmitter overflow after reserpine-pretreatment appears to be due to the decrease in the total release of the transmitter. 6. The results obtained support the view that in reserpine-pretreated tissues decreased transmitter output reduces the activation of the presynaptic α-adrenoceptors which mediate the negative feed-back mechanism that regulates transmitter release by nerve stimulation. PMID:4367125

  11. Preventive effect of insect tea against reserpine-induced gastric ulcers in mice

    PubMed Central

    ZHOU, YA-LIN; WANG, RUI; FENG, XIA; ZHAO, XIN

    2014-01-01

    The aim of the present study was to determine the preventive effect of insect tea against reserpine-induced gastric ulcers in ICR mice. A high (800 mg/kg) dose of insect tea reduced the serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with those in mice treated with a low (400 mg/kg) dose and the control mice. The serum levels of somatostatin (SS) and vasoactive intestinal peptide (VIP) in mice treated with insect tea were higher compared with those in the control mice; however, the serum levels of motilin (MOT) and substance P (SP) were lower in mice treated with insect tea than in the control mice. Gastric ulcer inhibitory rate of the insect tea treatment group of mice were much lower compared to the control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mice treated with insect tea were higher compared with those in control mice, and similar to those in normal mice and ranitidine-treated mice. The nitric oxide (NO) and maleic dialdehyde (MDA) levels of mice treated with a high concentration of insect tea compared with the normal group were close. Using quantitative polymerase chain reaction (qPCR) assays, the present study revealed that insect tea significantly induced inflammation in the tissues of mice by downregulating the expression of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and upregulating the expression of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α (IκB-α). These results suggest that insect tea is as effective at preventing gastric ulcers as the gastric ulcer drug, ranitidine and it can be used as medicine. PMID:25187847

  12. Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice.

    PubMed

    Liu, Shui-bing; Zhao, Rong; Li, Xu-sheng; Guo, Hong-ju; Tian, Zhen; Zhang, Nan; Gao, Guo-dong; Zhao, Ming-gao

    2014-06-01

    Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala. PMID:24584520

  13. Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats.

    PubMed

    Long, Lingli; Wang, Jingnan; Chen, Ningning; Zheng, Shuhui; Shi, Lanying; Xu, Yuxia; Luo, Canqiao; Deng, Yubin

    2016-06-01

    The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats. PMID:26872103

  14. Effect of the enzymatic inhibitor of Kunitz on the gastric lesions from reserpine, from phenylbutazone, from pyloric ligation and by restraint in the rat

    NASA Technical Reports Server (NTRS)

    Guerrin, F.; Demaille, A.; Merveille, P.; Bel, C.

    1980-01-01

    The protective effects of certain polypeptides on gastric ulcerations caused from reserpine and phenylbutazone in the rate were studied. It was found that the Kunitz enzymatic inhibitor exerts a protective action in regard to gastric lesions. However, the inhibitor did not change the development of Shay ulcers and stress ulcers from restraint.

  15. Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat.

    PubMed

    Antkiewicz-Michaluk, Lucyna; Wąsik, Agnieszka; Możdżeń, Edyta; Romańska, Irena; Michaluk, Jerzy

    2015-03-01

    Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2) and monoamine releaser, so it can be used as a pharmacological model of depression. In the present paper, we investigated the behavioral and neurochemical effects of withdrawal from acute and repeated administration of a low dose of reserpine (0.2 mg/kg) in Wistar Han rats. We demonstrated the behavioral and receptor oversensitivity (postsynaptic dopamine D1) during withdrawal from chronic reserpine. It was accompanied by a significant increase in motility in the locomotor activity test and climbing behavior in the forced swim test (FST). Neurochemical studies revealed that repeated but not acute administration the a low dose of reserpine triggered opposing adaptive changes in the noradrenergic and serotonin system function analyzed during reserpine withdrawal, i.e. 48 h after the last injection. The tissue concentration of noradrenaline was significantly decreased in the hypothalamus and nucleus accumbens only after repeated drug administration (by about 20% and 35% vs. control; p<0.05, respectively). On the other hand, the concentration of its extraneuronal metabolite, normetanephrine (NM) increased significantly in the VTA during withdrawal both from acute and chronic reserpine. The serotonin concentration was significantly reduced in the VTA after chronic reserpine (by about 40% vs. the control group, p<0.05) as well as its main metabolite, 5-HIAA (by about 30% vs. control; p<0.05) in the VTA and hypothalamus. Dopamine and its metabolites were not changed after acute or chronic reserpine administration. In vivo microdialysis studies clearly evidenced the lack of the effect of a single dose of reserpine, and its distinct effects after chronic treatment on the release of noradrenaline and serotonin in the rat striatum. In fact, the withdrawal from repeated administration of reserpine significantly increased an extraneuronal concentration of noradrenaline in the rat striatum but at the same

  16. Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers

    PubMed Central

    YI, RUOKUN; WANG, RUI; SUN, PENG; ZHAO, XIN

    2015-01-01

    Dragon-pearl tea is a type of green tea commonly consumed in Southwest China. In the present study, the antioxidative and anti-gastric ulcer effects of Dragon-pearl tea crude polyphenols (DTCP) were determined in vitro and in vivo. Treatment with 25, 50 or 100 µg/ml DTCP resulted in notable antioxidant effects in vitro, which manifested as 2,2-diphenyl-1-picrylhydrazyl and OH radical-scavenging activity. Furthermore, using an in vivo mouse model, DTCP was shown to reduce the gastric ulcer area in the stomach, in which the 200 mg/kg DTCP dose exhibited the most marked effect, with a gastric ulcer index inhibitory rate of 72.63%. In addition, DTCP was demonstrated to improve stomach acidity conditions in vivo by increasing the pH and reducing the level of gastric juice, as compared with the reserpine-induced gastric ulcer control mice. Furthermore, DTCP altered the serum levels of a number of oxidation-related biomolecules, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), lipid peroxidation (LPO) and catalase (CAT), to subsequently exert an anti-gastric ulcer effect. Treatment with 50, 100 and 200 mg/kg DTCP increased the SOD, GSH-Px and CAT levels and reduced the MDA and LPO levels in the mouse model of gastric ulcers. These serum level alterations resulted in the modified serum levels of prostaglandin E2 (PGE2) and nitric oxide (NO), which are associated with gastric mucosal protection. A reverse transcription-quantitative polymerase chain reaction (RT-PCR) assay is a molecular biology experiment which could determine the changes of mRNA in tissues. Using the RT-PCR assay, DTCP was observed to increase the mRNA expression levels of certain genes associated with gastric ulcers: Epidermal growth factor, epidermal growth factor receptor, vascular endothelial growth factor and vascular endothelial growth factor receptor 1, while reducing gastrin expression levels. Therefore, the results indicated that DTCP induced a marked

  17. Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice.

    PubMed

    Li, Gui-Jie; Sun, Peng; Wang, Rui; Zhou, Ya-Lin; Qian, Yu; Zhao, Xin

    2014-04-01

    This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-γ as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-κB, iNOS, and COX-2, and upregulating IκB-α. These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products. PMID:24757382

  18. Nitric oxide pathway activity modulation alters the protective effects of (-)Epigallocatechin-3-gallate on reserpine-induced impairment in rats.

    PubMed

    Chen, Cheng-Neng; Chang, Kuo-Chi; Lin, Rui-Feng; Wang, Mao-Hsien; Shih, Ruoh-Lan; Tseng, Hsiang-Chien; Soung, Hung-Sheng; Tsai, Cheng-Chia

    2016-05-15

    Reserpine (RES) has been reported to increase the brain's neural oxidative stress and cause cognitive dysfunction. Having powerful antioxidative properties, green tea catechins, especially (-)epigallocatechin-3-gallate (EGCG), are able to protect against many oxidative injuries. In this study, we examined the protecting properties of EGCG on RES-induced impairment of short-term memory in three-month-old male Wistar rats. RES (1mg/kg i.p.) induced memory impairment (p<0.001) as evaluated by the social recognition task. EGCG treatment (100mg/kg i.p. for 7days, starting 6days before RES injection) was able to improve the impaired memory caused by RES. RES treatment increased the nitric oxide (NO) level and lipid peroxidation (LPO) production, and decreased the antioxidation power in hippocampi. EGCG treatment was able to counteract the RES-induced NO level and LPO production, as well as enhanced the hippocampal antioxidation power in RES-treated rats. In order to examine the implication of NO pathway activity in RES treatment, either NO precursor (L-arginine; L-A) or NO synthase inhibitor (L-NAME; L-N) was co-pretreated with EGCG; NO precursor treatment eliminated the protective effect of EGCG, in contrast to that NO synthase inhibitor treatment significantly increased the EGCG effects on cognitive and biochemical protection in RES-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the RES-induced impairment, as well as in the protective effect of EGCG in treating RES-induced impairment of memory. The above evidence provides a clinically relevant value for EGCG in preventing RES-induced cognitive dysfunction. PMID:26944334

  19. Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice

    PubMed Central

    Li, Gui-Jie; Sun, Peng; Wang, Rui; Zhou, Ya-Lin; Qian, Yu

    2014-01-01

    This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-γ as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-κB, iNOS, and COX-2, and upregulating IκB-α. These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products. PMID:24757382

  20. Validated liquid chromatography-tandem mass spectrometry method for simultaneous determination of clopamide, reserpine and dihydroergotoxine: Application to pharmacokinetics in human plasma.

    PubMed

    Sharaf El-Din, Mohie M K; Nassar, Mohamed W I; Attia, Khalid A M; Demellawy, Maha A El; Kaddah, Mohamed M Y

    2016-06-01

    A simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the simultaneous quantitation of clopamide, reserpine and dihydroergotoxine (ergoloid mesylates) in human plasma. Under basic conditions, liquid-liquid extraction using ethyl acetate was efficiently used for extraction of the analytes from plasma samples in presence of indapamide as internal standard (IS). The analytes were separated with isocratic elution on Phenomenex(®) Synergi Fusion-RP 80A column (50×4.6mm, 4μm). With positive ion electrospray ionization (ESI), the analytes were quantified and monitored on a triple quadrupole mass spectrometer using Multiple Reaction Monitoring (MRM) scanning mode. Satisfactory results regarding linearity, recovery, stability, accuracy and precision of the analytes were obtained. The method was linear in the concentration range of 0.04-30.00ng/mL for reserpine, 1-96.00ng/mL for clopamide, and 0.05-40.00ng/mL for dihydroergotoxine alkaloids, respectively. For all analytes, the high sensitivity of HPLC-MS/MS method revealed sufficient lower limit of quantification (LLOQ) ranged from 0.04-1ng/mL using 1mL of plasma. The recoveries from spiked control samples were ≥86.16% for all analytes and IS. The intra- and inter-day precision variations were lower than 13.03% while the accuracy values ranged from 91.76% to 111.50%. The developed method was successfully applied to pharmacokinetic study of fixed dose combination of clopamide, reserpine and dihydroergotoxine in healthy male volunteers. PMID:27037980

  1. Evaluation of the Xpa-deficient transgenic mouse model for short-term carcinogenicity testing: 9-month studies with haloperidol, reserpine, phenacetin, and D-mannitol.

    PubMed

    Lina, Ben A R; Woutersen, Ruud A; Bruijntjes, Joost P; van Benthem, Jan; van den Berg, Jolanda A H; Monbaliu, Johan; Thoolen, Bob J J M; Beems, Rudolf B; van Kreijl, Coen F

    2004-01-01

    As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa-/- mice, Xpa-/-.p53+/- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D-mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D-mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D-mannitol were negative in the carcinogenicity assay with Xpa-/- and Xpa-/-.p53+/- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa-/-.p53+/- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans. PMID:15200157

  2. Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.

    PubMed

    Antkiewicz-Michaluk, Lucyna; Wąsik, Agnieszka; Możdżeń, Edyta; Romańska, Irena; Michaluk, Jerzy

    2014-07-01

    Animal models are widely used to study antidepressant-like effect in rodents. However, it should be mentioned that pharmacological models do not always take into account the complexity of the disease process. In the present paper, we demonstrated that repeated but not acute treatment with a low dose of reserpine (0.2 mg/kg i.p.) led to a pharmacological model of depression which was based on its inhibitory effect on the vesicular monoamine transporter 2, and monoamines depleting action in the brain. In fact, we observed that chronic treatment with a low dose of reserpine induced a distinct depressive-like behavior in the forced swim test (FST), and additionally, it produced a significant decrease in the level of dopamine, noradrenaline, and serotonin in the brain structures. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its close methyl derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are exo/endogenous amines present naturally in the mammalian brain which demonstrated a significant antidepressant-like effect in the FST and the reserpine model of depression in the rat. Both compounds, TIQ and 1MeTIQ, administered chronically in a dose of 25 mg/kg (i.p.) together with reserpine completely antagonized reserpine-produced depression as assessed by the immobility time and swimming time. Biochemical data were in agreement with behavioral experiments and demonstrated that chronic treatment with a low dose of reserpine in contrast to acute administration produced a significant depression of monoamines in the brain structures and impaired their metabolism. These neurochemical effects obtained after repeated reserpine (0.2 mg/kg i.p.) in the brain structures were completely antagonized by joint TIQ or 1MeTIQ (25 mg/kg i.p.) administration with chronic reserpine. A possible molecular mechanism of action of TIQ and 1MeTIQ responsible for their antidepressant action is discussed. On the basis of the presented behavioral and biochemical studies, we suggest that both

  3. Time course of the changes of TH mRNA in rat brain and adrenal medulla after a single injection of reserpine.

    PubMed Central

    Biguet, N F; Buda, M; Lamouroux, A; Samolyk, D; Mallet, J

    1986-01-01

    A single injection of reserpine causes a long lasting enhancement of the activity of tyrosine hydroxylase (TH), the enzyme catalyzing the rate-limiting step in the biosynthesis of catecholamines. A sensitive method has been developed to assay both TH mRNA level and enzyme activity in tissue from a single rat. The time course of the induction was analysed in adrenals, locus coeruleus and substantia nigra. In both locus coeruleus and adrenals reserpine caused respectively 4.2- and 4.5-fold increase of TH mRNA which was maximal 2 days after drug injection. This increase is about twice that of the enzyme activity. No change was observed in substantia nigra. The effect lasted longer in locus coeruleus than in adrenal. In the latter, TH mRNA had almost returned to initial values at day 4 whereas at this time it is 3-fold higher in locus coeruleus and still significant at day 18. This result suggests that induction of TH results from an enhanced transcription of the TH gene. The time course difference between locus coeruleus and adrenals is most likely to result from a difference in the stability of TH mRNA in the two structures. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2872048

  4. Effects of reserpine and L-cysteine and glutathione depletion on 2-bromoethylamine hydrobromide-induced tubular necrosis in Swiss ICR mice.

    PubMed

    Wolf, D C; Carlson, G P; DeNicola, D B; Carlton, W W

    1991-08-01

    Female Swiss ICR mice were injected ip with 100 or 300 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight. Male Swiss ICR mice were subjected to water deprivation, or treated with 5% dextrose in water, dimethylsulphoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, beta-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulphoximine or L-cysteine. Urine collected sequentially from male Swiss ICR mice given 300 mg BEA/kg body weight was analysed for glucose, protein, pH and specific gravity. Female mice were less sensitive to BEA than were male mice. Diuresis, antidiuresis, treatment with cytochrome P-450 inducers and inhibitors, and the antioxidant dimethyl-sulphoxide had no effect on the incidence or severity of tubular necrosis (TN) induced by BEA. Probenecid and L-cysteine decreased the severity, but they had no effect on the incidence of TN. Glutathione depletion by diethyl maleate and inhibition of glutathione synthesis by buthionine sulphoximine decreased the dose of BEA necessary to cause TN; buthionine sulphoximine was more effective than diethyl maleate. Reserpine decreased both the incidence and severity of TN. Glycosuria, aciduria and decreased urinary specific gravity occurred before morphological changes were seen under the microscope, indicating that the functional changes precede the morphological changes. These data indicate that glutathione is important in protecting against BEA-induced TN, that BEA or a metabolite is concentrated in the tubule epithelium by way of anion transport, and that vasoconstriction contributes to the development of BEA-induced TN. PMID:1894223

  5. Comparison of the Efficiency of Adeprophen and Antidepressants of Various Groups on the Model of Reserpine-Induced Depression in Rats.

    PubMed

    Ozerov, A A; Bagmetova, V V; Chernysheva, Yu V; Tyurenkov, I N

    2016-03-01

    A new (aryloxyalkyl)adenine derivative Adeprophen (9-[2-(4-isopropylphenoxy)ethyl]adenine, VMA-99-82) has a strong antidepressant effect on the model of reserpine-induced depression in rats (single dose 4 mg/kg, intraperitoneally). This effect manifested in suppression of depression-like behavior in the Porsolt forced swimming test (shortening of immobility time and increase in immobility latency, number of jumping episodes, and time of active swimming) and sucrose consumption/preference test (increase in the consumption of 20% sucrose solution in g/100 g body weight and percentage of sucrose preference in relation to the total fluid preference). Adeprophen had a greater antidepressant effect than sertraline and fluoxetine, but was less potent than amitriptyline, imipramine, venlafaxine, and to a lesser extent to paroxetine. PMID:27021092

  6. [Plasma ACTH, STH and other hormone levels in various groups under chlormethiazole, haloperidol or reserpine load in alchohol delirium, alcoholic hallucinations, and chronic alcoholism].

    PubMed

    Dobrzański, T; Pieschl, D

    1976-01-01

    Studies of 135 men with safely diagnosed alcohol delirium mostly revealed increased ACTH blood values when sober and increased T4 values in about 1/3 of these patients. There is a correlation between the psychiatric clinical picture of the alcohol delirium and the ACTH content of the plasma. Under load with chloromethiazole, halperidole or with reserpine, there is a significant drop in the increased ACTH and T4 values. In an acute alcoholic hallucinosis (n=16) similar endocrinological changes as in most cases of safely diagnosed alcohol delirium were observed. In a chronic alcoholic hallucinosis (n=11) and in chronic alcoholics (n=31) the endocrinological values were similar to those of patients after alcohol delirium. PMID:181772

  7. Nano-structured complexes of reserpine and quinidine drugs with chloranilic acid based on intermolecular H-bond: Spectral and surface morphology studies

    NASA Astrophysics Data System (ADS)

    Adam, Abdel Majid A.

    2014-06-01

    The study of the drug-acceptor interaction may be useful in understanding the drug-receptor interactions and the mechanism of drug action. Here, complexes of reserpine (Res) and quinidine (Qui) drugs with chloranilic acid (CLA) have been synthesized. Then, these complexes were characterized chemically and structurally using CHN elemental analysis, infrared (IR) and electronic absorption spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The stoichiometry of the H-bonded complex was found to have a 1:1 ratio, so these complexes can be formulated as [(Drug)(CLA)]. IR measurements confirmed the presence of intermolecular H-bond. Application of Debye-Scherrer equation indicates that the formed complexes are in the range of nano-size. The Res complex exhibits a remarkable crystalline morphology. It was also found that the particle size of Res complex is 1.533 time higher than that of Qui complex. Interestingly, free Res molecular weight is higher than that of free Qui by the same ratio (precisely; 1.525).

  8. The laser desorption/laser ionization mass spectra of some indole derivatives and alkaloids

    NASA Astrophysics Data System (ADS)

    Rogers, Kevin; Milnes, John; Gormally, John

    1992-06-01

    The laser desorption and laser ionization mass spectra of some indole derivatives and alkaloids are described with particular reference to their modes of fragmentation. Mass spectra of yohimbine, reserpine, quinine and quinidine are presented. Full experimental details are given.

  9. Impaired Ranvier node sodium-potassium adenosine triphosphatase may induce facial palsy.

    PubMed

    Kanoh, N; Sakagami, M

    1996-09-01

    To clarify the part of the neuron essential for myelinated nerve conduction, the cytochemical localization of potassium ion (K+)-dependent p-nitrophenylphosphatase (K-NPPase) activity was investigated in the normal and reserpine-treated facial nerve of guinea pigs. In the normal animals, K-NPPase activity was localized to the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, enzyme activity was observed along the paranodal and nodal axolemma. In reserpinized nerves, K-NPPase activity was absent along the internodal axolemma and Schmidt-Lanterman incisures. In the Ranvier nodes, however, enzyme activity was detectable only in the nodal axolemma. The reserpinized animals demonstrated no evidence of facial palsy. Because K-NPPase is essential for nerve conduction, these results indicate that the location of enzyme activity in reserpinized animals, namely the nodal axolemma, may be of prime importance in saltatory nerve conduction. PMID:8822727

  10. [The effect of some pharmacological agents and electroshock on the level of cyclic AMP of the total mouse brain].

    PubMed

    Joanny, P; Devolx, B C; Garron, J; Giannellini, F

    1976-01-01

    Amphetamin, pentobarbital, pargyline, parachlorophenylalanine, pentetrasol and maximal electroshock all increased significantly cyclic AMP in mice whole brain conversely reserpine induced a decrease of cyclic nucleotide. All those changes were tentatively correlated toward central monoaminergic systems activation. PMID:192423

  11. Sotalol

    MedlinePlus

    ... especially medications for migraine headaches, diabetes, asthma, allergies, colds, or pain; other medications for high blood pressure or heart disease; reserpine; and vitamins.if you are taking aluminum- or magnesium-containing antacids (Maalox, Mylanta), take them ...

  12. Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.

    PubMed

    Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Duplancic, B; Marovic, A; Zoricic, I; Prkacin, I; Lovric-Bencic, M; Aralica, G; Ziger, T; Perovic, D; Jelovac, N; Dodig, G; Rotkvic, I; Mise, S; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

    2000-01-01

    Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either

  13. Brain α2-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA

    PubMed Central

    Ribas, Catalina; Miralles, Antonio; Busquets, Xavier; García-Sevilla, Jesús A

    2001-01-01

    This study was designed to assess the molecular and cellular events involved in the up-regulation (and receptor supersensitivity) of brain α2-adrenoceptors as a result of chronic depletion of noradrenaline (and other monoamines) by reserpine. Chronic reserpine (0.25 mg kg−1 s.c., every 48 h for 6 – 14 days) increased significantly the density (Bmax values) of cortical α2-adrenoceptor agonist sites (34 – 48% for [3H]-UK14304, 22 – 32% for [3H]-clonidine) but not that of antagonist sites (11 – 18% for [3H]-RX821002). Competition of [3H]-RX821002 binding by (−)-adrenaline further indicated that chronic reserpine was associated with up-regulation of the high-affinity state of α2-adrenoceptors. In cortical membranes of reserpine-treated rats (0.25 mg kg−1 s.c., every 48 h for 20 days), the immunoreactivities of various G proteins (Gαi1/2, Gαi3, Gαo and Gαs) were increased (25 – 34%). Because the high-affinity conformation of the α2-adrenoceptor is most probably related to the complex with Gαi2 proteins, these results suggested an increase in signal transduction through α2-adrenoceptors (and other monoamine receptors) induced by chronic reserpine. After α2-adrenoceptor alkylation, the analysis of receptor recovery (Bmax for [3H]-UK14304) indicated that the increased density of cortical α2-adrenoceptors in reserpine-treated rats was probably due to a higher appearance rate constant of the receptor (Δr=57%) and not to a decreased disappearance rate constant (Δk=7%). Northern- and dot-blot analyses of RNA extracted from the cerebral cortex of saline- and reserpine-treated rats (0.25 mg kg−1, s.c., every 48 h for 20 days) revealed that reserpine markedly increased the expression of α2a-adrenoceptor mRNA in the brain (125%). This transcriptional activation of the receptor gene expression appears to be the cellular mechanism by which reserpine induces up-regulation in the density of brain α2-adrenoceptors

  14. Magnesium Supplementation Prevents and Reverses Experimentally Induced Movement Disturbances in Rats: Biochemical and Behavioral Parameters.

    PubMed

    Kronbauer, Maikel; Segat, Hecson J; De David Antoniazzi, Caren Tatiane; Roversi, Karine; Roversi, Katiane; Pase, Camila S; Barcelos, Raquel C S; Burger, Marilise E

    2015-08-01

    Reserpine administration results in a predictable animal model of orofacial dyskinesia (OD) that has been largely used to access movement disturbances related to extrapyramidal oxidative damage. Here, OD was acutely induced by reserpine (two doses of 0.7 mg/kg subcutaneous (s.c.)), every other day for 3 days), which was administered after (experiment 1) and before (experiment 2) magnesium (Mg) supplementation (40 mg/kg/mL, peroral (p.o.)). In experiment 1, Mg was administered for 28 days before reserpine treatment, while in experiment 2, it was initiated 24 h after the last reserpine administration and was maintained for 10 consecutive days. Experiment 1 (prevention) showed that Mg supplementation was able to prevent reserpine-induced OD and catalepsy development. Mg was also able to prevent reactive species (RS) generation, thus preventing increase of protein carbonyl (PC) levels in both cortex and substantia nigra, but not in striatum. Experiment 2 (reversion) showed that Mg was able to decrease OD and catalepsy at all times assessed. In addition, Mg was able to decrease RS generation, with lower levels of PC in both cortex and striatum, but not in substantia nigra. These outcomes indicate that Mg is an important metal that should be present in the diet, since its intake is able to prevent and minimize the development of movement disorders closely related to oxidative damage in the extrapyramidal brain areas, such as OD. PMID:25686766

  15. Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

    PubMed

    Trevizol, Fabiola; Benvegnú, Dalila M; Barcelos, Raquel C S; Pase, Camila S; Segat, Hecson J; Dias, Verônica Tironi; Dolci, Geisa S; Boufleur, Nardeli; Reckziegel, Patrícia; Bürger, Marilise E

    2011-08-01

    Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal. PMID:21356248

  16. X-ray microanalysis of exocrine glands in animal models for cystic fibrosis

    SciTech Connect

    Mueller, R.M.R.; Roomans, G.M.

    1985-01-01

    Elemental distribution and ultrastructure of the submandibular gland, the parotid gland and the pancreas were investigated in three suggested animal models of the disease cystic fibrosis: the chronically reserpinized rat, the chronically isoproterenol-treated rat, and the chronically pilocarpine-treated rat. To elucidate the cellular mechanism underlying the effects of these treatments, chronic effects of specific alpha - and beta -adrenergic agonists, as well as acute effects of reserpine and various agonists were also investigated. Reserpine, isoproterenol, and pilocarpine cause an increase in the calcium concentration in submandibular gland acinar cells, due to an increased calcium content of the intracellular mucus. In the parotid gland, reserpine and isoproterenol cause a decrease of the calcium concentration in acinar cells, due to a lower calcium content of the zymogen granules. In the submandibular gland, a decreased cellular Na concentration was noted after chronic treatment with isoproterenol or pilocarpine, and after a single dose of reserpine or isoproterenol. Ultrastructural changes in the exocrine glands investigated included excessive accumulation of intracellular secretory material and formation of abnormal uncondensed secretion granules. A common pattern in the animal models appears to be (1) inhibition of secretion resulting in intracellular accumulation of secretory material, (2) synthesis of secretory macromolecules with altered cation-binding properties.

  17. The role of brain biogenic amines in the control of pituitary-adrenocortical activity

    NASA Technical Reports Server (NTRS)

    Maickel, R. P.

    1975-01-01

    It was found that pretreatment of animals with desmethyl imipramine antagonized the reserpine-induced sedation without preventing the decline in brain amines or the hypersecretion of adrenocorticotropic hormone (ACTH). The antagonism of reserpine-induced ACTH hypersecretion by the monoamine oxidose (MAO) inhibitor pargyline (MO 911, N-methyl-N-benzyl-2-propynylamine) was studied. Evidence is presented that this antagonism is related to the level of brain biogenic amines maintained during the course of action of the drug. Pretreatment with MAO inhibitors does not affect the ACTH hypersecretion evoked by exposure to cold or chlorpromazine, lending further support to the hypothesis that reserpine-induced ACTH hypersecretion is related to brain amine changes.

  18. [The characteristics of the restructuring of the circadian dynamics in rat motor activity in response to a phase shift in the photoperiod in the experimental modelling of depression].

    PubMed

    Baturin, V A; Arushanian, E B

    1994-01-01

    Gradual reorganization of the locomotor activity of rats after a shift in the photoperiod was disrupted under the influence of depressogenic agents (reserpine or chronic pain stress). After the chronic use of the antidepressant amitriptyline the disruption of the reorganization of the daily motor activity typical for reserpine was not observed confirming a specificity of these changes. The results suggest that in the experimental model of depression there arise conditions for functional disturbance of the circadian pacemaker and an increase of sensitivity to the photic Zeitgeber. PMID:7941725

  19. Cellular potentials, electrogenic sodium pumping and sensitivity in guinea-pig atria.

    PubMed

    Schulz, J C; Fleming, W W; Westfall, D P; Millecchia, R

    1984-10-01

    Intracellular recording techniques in guinea-pig atrial pacemaker and nonpacemaker cells were used to investigate 1) the role of membrane potential changes in postjunctional supersensitivity, 2) the electrogenicity of the Na+,K+ pump and 3) the role of electrogenic pumping in sensitivity of the atria to agonists. In nonpacemaker cells, ouabain (10(-6) M) had no effect on resting membrane potential (left atria) or maximum diastolic potential (right atria). However, ouabain effectively suppressed the transient hyperpolarization that followed cessation of electrical stimulation. In pacemaker cells, ouabain and chronic treatment with reserpine (0.1 mg/kg/day) produced quite different patterns of changes in intracellular potentials. Chronic treatment with reserpine induced chronotropic supersensitivity to isoproterenol but not to histamine. Ouabain did not alter the chronotropic sensitivity to either agonist. The effects of isoproterenol and histamine on intracellular potentials in pacemaker cells were investigated in the presence and absence of ouabain and in control atria vs. atria from guinea pigs chronically pretreated with reserpine. Analysis of the data indicated that 1) electrophysiological measurements do not provide a discernible explanation for chronotropic supersensitivity, 2) the Na+ pump has the capacity for electrogenic pumping under conditions of Na+ loading, but demonstrates little indication of electrogenicity under basal conditions and 3) chronic treatment with reserpine does suppress the Na+,K+ pump in some areas of the right atrium, but this activity probably does not contribute to chronotropic supersensitivity. Other possible mechanisms of postjunctional supersensitivity in atria are discussed. PMID:6491974

  20. Fluorescence lifetimes of some Rauwolfia alkaloids

    NASA Astrophysics Data System (ADS)

    Hidalgo, J.; Arjona, D. Gonzalez; Roldan, E.; Sanchez, M.

    1986-03-01

    The natural fluorescence lifetimes of the following Rauwolfia alkaloids, Reserpine, Rescinnamine, Corynanthine, Yohimbine, --- Ajmalicine, Serpentine and Ajmaline, have been calculated from a modified form of the Strickler-Berg equation. The actual lifetimes were derived from the quantum yields and the calculated natural lifetimes.

  1. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats.

    PubMed

    Xue, Rui; He, Xin-Hua; Yuan, Li; Chen, Hong-Xia; Zhang, Li-Ming; Yong, Zheng; Yu, Gang; Fan, Shi-Yong; Li, Yun-Feng; Zhong, Bo-Hua; Zhang, You-Zhi

    2016-01-01

    Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS) model. Results in pharmacological models indicated that acute administration of 071031B at 5-20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo. PMID:26318675

  2. Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

    PubMed

    Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

    2016-02-26

    Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. PMID:26806036

  3. Quantification and characterization of alkaloids from roots of Rauwolfia serpentina using ultra high performance liquid chromatography-photo diode array-mass spectrometry (UHPLC-PDA-MS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The roots of Rauwolfia serpentina (L.) Benth. ex Kurz has been used in native Indian medicine for treatment of various illnesses and has been mainly used to treat hypertension. Reserpine is potent substance which shared both central nervous system depressant and hypotensive actions. An UHPLC-UV meth...

  4. Neuroprotective effect of EGb761® and low-dose whole-body γ-irradiation in a rat model of Parkinson's disease.

    PubMed

    El-Ghazaly, Mona A; Sadik, Nermin A H; Rashed, Engy R; Abd-El-Fattah, Amal A

    2015-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body γ-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body γ-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose γ-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of γ-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels. PMID:23696346

  5. Injection of Resperpine into Zebrafish, Prevents Fish to Fish Communication of Radiation-Induced Bystander Signals: Confirmation in Vivo of a Role for Serotonin in the Mechanism

    PubMed Central

    Saroya, Rohin; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2009-01-01

    Serotonin (5-HT) has been implicated as a potential modulator of the bystander effect in cell cultures. To assess the relevance of serotonin in vivo experiments were done with the zebrafish (Danio rerio). This species, when irradiated, transmits bystander signals to non-irradiated fish. The animals were injected with reserpine, an inhibitor of serotonin at a dose of 80mg/kg of body mass. The results show that reserpine treated fish had only 27% of the serotonin in non-treated fish. Skin tissue samples were collected from the fish and assayed for bystander signal production using a reporter bioassay. Reserpine prevented the production and communication of signals between fish. Intracellular calcium flux, identified as a bystander response in the reporter cells confirmed this. Medium harvested from tissues of X-rayed fish and their bystanders, showed an oscillating pattern of calcium flux. Samples from X-rayed fish pretreated with reserpine produced a chaotic pattern of random fluctuations in the reporter cells, while their bystander fish led to increased calcium, but no oscillations. These results suggest that 5-HT is involved in bystander signalling in zebrafish, and by decreasing the amount of available 5-HT the bystander effect can be blocked. PMID:20877486

  6. Cooperation between prokaryotic (Lde) and eukaryotic (MRP) efflux transporters in J774 macrophages infected with Listeria monocytogenes: studies with ciprofloxacin and moxifloxacin.

    PubMed

    Lismond, Ann; Tulkens, Paul M; Mingeot-Leclercq, Marie-Paule; Courvalin, Patrice; Van Bambeke, Françoise

    2008-09-01

    Antibiotic efflux is observed in both eukaryotic and prokaryotic cells, modulating accumulation and resistance. The present study examines whether eukaryotic and prokaryotic fluoroquinolone transporters can cooperate in the context of an intracellular infection. We have used (i) J774 macrophages (comparing a ciprofloxacin-resistant cell line overexpressing an MRP-like transporter with wild-type cells with basal expression), (ii) Listeria monocytogenes (comparing a clinical isolate [CLIP21369] displaying ciprofloxacin resistance associated with overexpression of the Lde efflux system with a wild-type strain [EGD]), (iii) ciprofloxacin (substrate of both Lde and MRP) and moxifloxacin (nonsubstrate), and (iv) probenecid and reserpine (preferential inhibitors of MRP and Lde, respectively). The ciprofloxacin MICs for EGD were unaffected by reserpine, while those for CLIP21369 were decreased approximately fourfold (and made similar to those of EGD). Neither probenecid nor reserpine affected the moxifloxacin MICs against EGD or CLIP21369. In dose-response studies (0.01x to 100x MIC) in broth, reserpine fully restored the susceptibility of CLIP21369 to ciprofloxacin (no effect on EGD) but did not influence the activity of moxifloxacin. In studies with intracellular bacteria, reserpine, probenecid, and their combination increased the activity of ciprofloxacin in wild-type and ciprofloxacin-resistant macrophages in parallel with an increase in ciprofloxacin accumulation in macrophages for EGD and an increase in accumulation and decrease in MIC (in broth) for CLIP21369. Moxifloxacin accumulation and intracellular activity were consistently not affected by the inhibitors. A bacterial efflux pump may thus actively cooperate with a eukaryotic efflux transporter to reduce the activity of a common substrate (ciprofloxacin) toward an intracellular bacterial target. PMID:18573933

  7. Stereochemistry of C7-allyl yohimbine explored by X-ray crystallography

    NASA Astrophysics Data System (ADS)

    Kagawa, Natsuko; Masuda, Yoshitake; Morimoto, Tsumoru; Kakiuchi, Kiyomi

    2013-03-01

    X-ray crystallographic analysis revealed that the palladium-catalyzed β-allylation of yohimbine proceeded in a (7S)-selective manner. The crystal structure had an indolenine unit that was generally unstable in air. A stereoselective outcome was obtained when the palladium π-allyl complex approached yohimbine from the less-hindered pro-S side. However, during reserpine allylation—because the structure of reserpine is that of a transoid-3, 15-ring junction—the palladium π-allyl complex approached from both sides: pro-S and pro-R. A computational method was developed to discuss this selectivity. Experimental details and considerations of the reaction are provided.

  8. Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice.

    PubMed

    Yin, Cui; Gou, Lingshan; Liu, Yi; Yin, Xiaoxing; Zhang, Ling; Jia, Genguang; Zhuang, Xuemei

    2011-11-01

    L-theanine (γ-glutamylethylamide), an amino acid component of green tea, has been shown to reduce mental and physical stress, and to improve memory function. In this study, the antidepressant effect of L-theanine was investigated in mice using the forced swim test, tail suspension test, open-field test and reserpine test. L-theanine produced an antidepressant-like effect, since the administration of L-theanine at doses of 1, 4 and 20 mg/kg for 10 successive days significantly reduced the immobility time in both the forced swim test and tail suspension test, compared with the control group, without accompanying changes in ambulation in the open-field test. Moreover, L-theanine significantly antagonized reserpine-induced ptosis and hypothermia. Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system. PMID:21425373

  9. Anti-ulcer effect of the hot water extract of black tea (Camellia sinensis).

    PubMed

    Maity, S; Vedasiromoni, J R; Ganguly, D K

    1995-06-01

    The effect of the hot water extract of black tea (Camellia sinensis (L.) O. Kuntze, Theaceae) on ulceration induced by various ulcerogens and by cold restraint stress (CRS) was investigated in albino rats. While prior administration of tea extract for 7 days significantly reduced the incidence of ulcer, ulcer number and ulcer index produced by aspirin, indomethacin, ethanol, reserpine and CRS, it failed to inhibit the ulcers induced by serotonin and histamine. Tea extract also favourably altered the changes in acid and peptic activity of gastric secretion induced by aspirin, indomethacin, ethanol, reserpine and CRS. The observations suggest that the hot water extract of black tea possesses anti-ulcer activity, probably mediated through prostaglandins. PMID:7564415

  10. Alpha-amylase circadian rhythm of young rat parotid gland: an endogenous rhythm with maternal coordination.

    PubMed

    Bellavía, S L; Sanz, E G; Sereno, R; Vermouth, N T

    1992-01-01

    The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. alpha-1,4-glucan-4-glucanohydrolase) in the parotid glands of 25-day-old rats were studied under different experimental designs (fasting, reversed photoperiod, constant lighting conditions and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of fasted rats did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm was present, with changes in the acrophase, in parotids of rats kept during their gestation and postnatal life in constant light or dark. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, and with maternal coordination. PMID:1610312

  11. Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?

    PubMed

    Sia, T C; Flack, N; Robinson, L; Kyloh, M; Nicholas, S J; Brookes, S J; Wattchow, D A; Dinning, P; Oliver, J; Spencer, N J

    2013-06-14

    Recent studies have shown genetic deletion of the gene that synthesizes 5-HT in enteric neurons (tryptophan hydroxylase-2, Tph-2) leads to a reduction in intestinal transit. However, deletion of the Tph-2 gene also leads to major developmental changes in enteric ganglia, which could also explain changes in intestinal transit. We sought to investigate this further by acutely depleting serotonin from enteric neurons over a 24-h period, without the confounding influences induced by genetic manipulation. Guinea-pigs were injected with reserpine 24h prior to euthanasia. Video-imaging and spatio-temporal mapping was used to record peristalsis evoked by natural fecal pellets, or slow infusion of intraluminal fluid. Immunohistochemical staining for 5-HT was used to detect the presence of serotonin in the myenteric plexus. It was found that endogenous 5-HT was always detected in myenteric ganglia of control animals, but never in guinea-pigs treated with reserpine. Interestingly, peristalsis was still reliably evoked by either intraluminal fluid, or fecal pellets in reserpine-treated animals that also had their entire mucosa and submucosal plexus removed. In these 5-HT depleted animals, there was no change in the frequency of peristalsis or force generated during peristalsis. In control animals, or reserpine treated animals, high concentrations (up to 10 μM) of ondansetron and SDZ-205-557, or granisetron and SDZ-205-557 had no effect on peristalsis. In summary, acute depletion of serotonin from enteric nerves does not prevent distension-evoked peristalsis, nor propulsion of luminal content. Also, we found no evidence that 5-HT3 and 5-HT4 receptor activation is required for peristalsis, or propulsion of contents to occur. Taken together, we suggest that the intrinsic mechanisms that generate peristalsis and entrain propagation along the isolated guinea-pig distal colon are independent of 5-HT in enteric neurons or the mucosa, and do not require the activation of 5-HT3 or 5

  12. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Wyllie, R. G.; Hill, G. S.; Murray, G.; Ramsden, P. W.; Heptinstall, R. H.

    1972-01-01

    Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4114974

  13. Nondiscriminated avoidance of shock by pigeons pecking a key1

    PubMed Central

    Ferrari, Elenice A.; Todorov, João Claudio; Graeff, Frederico Guilherme

    1973-01-01

    Four pigeons were trained to avoid shock by pecking a key on a free-operant avoidance schedule in which no exteroceptive stimulus signalled impending shock. Response rate was an inverse function of response-shock interval when shock-shock interval was held constant at 2 sec and response-shock intervals varied from 5 to 40 sec. Amphetamine increased response rates in two subjects and reserpine markedly reduced responding in one. PMID:16811659

  14. Side effects in the neonate from psychotropic agents excreted through breast-feeding.

    PubMed

    Ananth, J

    1978-07-01

    Neuroleptics, antidepressants, lithium, anxiolytics, and hypnotics may be excreted in breast milk. Because of the danger to the neonate, drugs such as diazepam, lithium, bromides, reserpine, and opium alkaloids should not be given to lactating women, and barbiturates, haloperidol, and penfluridol should be administered with caution. The side effects produced as a result of breast-feeding of the infant by mothers consuming psychotropic drugs are reviewed and possible preventive measures are discussed. PMID:665791

  15. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression.

    PubMed

    Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan; Cheng, Tain-Junn; Chuu, Jiunn-Jye

    2015-01-01

    Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression. PMID:26114099

  16. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    PubMed Central

    Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan

    2015-01-01

    Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression. PMID:26114099

  17. Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells: relevance to the pathogenesis of Parkinson's disease.

    PubMed

    Goldstein, David S; Sullivan, Patti; Cooney, Adele; Jinsmaa, Yunden; Sullivan, Rachel; Gross, Daniel J; Holmes, Courtney; Kopin, Irwin J; Sharabi, Yehonatan

    2012-12-01

    Parkinson's disease entails profound loss of nigrostriatal dopaminergic terminals, decreased vesicular uptake of intraneuronal catecholamines, and relatively increased putamen tissue concentrations of the toxic dopamine metabolite, 3,4-dihydroxyphenylacetaldehyde (DOPAL). The objective of this study was to test whether vesicular uptake blockade augments endogenous DOPAL production. We also examined whether intracellular DOPAL contributes to apoptosis and, as α-synuclein oligomers may be pathogenetic in Parkinson's disease, oligomerizes α-synuclein. Catechols were assayed in PC12 cells after reserpine to block vesicular uptake, with or without inhibition of enzymes metabolizing DOPAL-daidzein for aldehyde dehydrogenase and AL1576 for aldehyde reductase. Vesicular uptake was quantified by a method based on 6F- or (13) C-dopamine incubation; DOPAL toxicity by apoptosis responses to exogenous dopamine, with or without daidzein+AL1576; and DOPAL--induced synuclein oligomerization by synuclein dimer production during DOPA incubation, with or without inhibition of L-aromatic-amino-acid decarboxylase or monoamine oxidase. Reserpine inhibited vesicular uptake by 95-97% and rapidly increased cell DOPAL content (p = 0.0008). Daidzein+AL1576 augmented DOPAL responses to reserpine (p = 0.004). Intracellular DOPAL contributed to dopamine-evoked apoptosis and DOPA-evoked synuclein dimerization. The findings fit with the 'catecholaldehyde hypothesis,' according to which decreased vesicular sequestration of cytosolic catecholamines and impaired catecholaldehyde detoxification contribute to the catecholaminergic denervation that characterizes Parkinson's disease. PMID:22906103

  18. Control of Analyte Electrolysis in Electrospray Ionization Mass Spectrometry Using Repetitively Pulsed High Voltage

    SciTech Connect

    Kertesz, Vilmos; Van Berkel, Gary J

    2011-01-01

    Analyte electrolysis using a repetitively pulsed high voltage ion source was investigated and compared to that using a regular, continuously operating direct current high voltage ion source in electrospray ionization mass spectrometry. The extent of analyte electrolysis was explored as a function of the length and frequency of the high voltage pulse using the model compound reserpine in positive ion mode. Using +5 kV as the maximum high voltage amplitude, reserpine was oxidized to its 2, 4, 6 and 8-electron oxidation products when direct current high voltage was employed. In contrast, when using a pulsed high voltage, oxidation of reserpine was eliminated by employing the appropriate high voltage pulse length and frequency. This effect was caused by inefficient mass transport of the analyte to the electrode surface during the duration of the high voltage pulse and the subsequent relaxation of the emitter electrode/ electrolyte interface during the time period when the high voltage was turned off. This mode of ESI source operation allows for analyte electrolysis to be quickly and simply switched on or off electronically via a change in voltage pulse variables.

  19. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.

    PubMed

    Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V

    1999-12-01

    The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP. PMID:10672997

  20. The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine, and glutamate in the striatum of rats with altered function of VMAT2.

    PubMed

    Gołembiowska, Krystyna; Dziubina, Anna

    2012-08-01

    It has been shown that a decreased vesicular monoamine transporter (VMAT2) function and the disruption of dopamine (DA) storage is an early contributor to oxidative damage of dopamine neurons in Parkinson's disease (PD). In our previous study, we demonstrated that adenosine A(2A) receptor antagonists suppressed oxidative stress in 6-hydroxydopamine-treated rats suggesting that this effect may account for neuroprotective properties of drugs. In the present study, rats were injected with reserpine (10 mg/kg sc) and 18 h later the effect of the adenosine A(2A) receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on extracellular DA, glutamate and hydroxyl radical formation was studied in the rat striatum using in vivo microdialysis. By disrupting VMAT2 function, reserpine depleted DA stores, and increased glutamate and hydroxyl radical levels in the rat striatum. CSC (1 mg/kg) but not ZM 241385 (3 mg/kg) increased extracellular DA level and production of hydroxyl radical in reserpinised rats. Both antagonists decreased the reserpine-induced increase in extracellular glutamate. L-3,4-Dihydroxyphenylalanine (L-DOPA) (25 mg/kg) significantly enhanced extracellular DA, had no effect on reserpine-induced hydroxyl radical production and decreased extracellular glutamate concentration. CSC but not ZM 241385 given jointly with L-DOPA increased the effect of L-DOPA on extracellular DA and augmented the reserpine-induced hydroxyl radical production. CSC and ZM 241385 did not influence extracellular glutamate level, which was decreased by L-DOPA. It seems that by decreasing the MAO-dependent DA metabolism rate, CSC raised cytosolic DA and by DA autoxidation, it induced hydroxyl radical overproduction. Thus, the methylxanthine A(2A) receptor antagonists bearing properties of MAO-B inhibitor, like CSC, may cause a risk of oxidative stress resulting from dysfunctional DA storage

  1. Phytotherapy of experimental depression: Kalanchoe integra Var. Crenata (Andr.) Cuf Leaf Extract

    PubMed Central

    Kukuia, Kennedy K. E.; Asiedu-Gyekye, Isaac J.; Woode, Eric; Biney, Robert P.; Addae, Emmanuel

    2015-01-01

    Context: Kalanchoe sp. have been used since 1921 for central nervous system (CNS) disorders such as psychosis and depression. It is known to possess CNS depressant effects. Aims: To investigate the antidepressant properties of the aqueous leaf extract of Kalanchoe integra. Settings and Design: The study was carried out at the Kwame Nkrumah University of Science and Technology between 6 a.m. and 3 p.m. Materials and Methods: ICR mice were subjected to the forced swimming test (FST) and tail suspension test (TST) after they had received extract (30-300 mg/kg), fluoxetine (3-30 mg/kg), desipramine (3-30 mg/kg) orally, or water (as vehicle). In a separate experiment, mice were pre-treated with reserpine (1 mg/kg), α-methyl paratyrosine (AMPT; 400 mg/kg), both reserpine (1 mg/kg) and AMPT (200 mg/kg) concomitantly, or p-chlorophenylalanine (pCPA; 200 mg/kg) to ascertain the role of the noradrenergic and serotoninergic systems in the mode of action of the extract. Statistical analysis used: Means were analyzed by analysis of variance (ANOVA) followed by Newman-Keuls’ post hoc test. P < 0.05 was considered significant. Results: In both FST and TST, the extract induced a decline in immobility, indicative of antidepressant-like effect. This diminution in immobility was reversed by pCPA, but not by reserpine and/or AMPT. The extract increased the swimming and climbing scores in the FST, suggestive of possible interaction with serotoninergic and noradrenergic systems. In the TST, the extract produced increases in both curling and swinging scores, suggestive of opioidergic monoaminergic activity, respectively. Conclusions: The present study has demonstrated the antidepressant potential of the aqueous leaf extract of K. integra is mediated possibly by a complex interplay between serotoninergic, opioidergic, and noradrenergic systems. PMID:25709333

  2. Identification, characterization and distribution of monoterpene indole alkaloids in Rauwolfia species by Orbitrap Velos Pro mass spectrometer.

    PubMed

    Kumar, Sunil; Singh, Awantika; Bajpai, Vikas; Kumar, Brijesh

    2016-01-25

    Monoterpene indole alkaloids (MIAs) are medicinally important class of compounds abundant in the roots of Rauwolfia species (Apocynaceae). MIAs such as yohimbine (aphrodisiac agent) and reserpine (antihypertensive, tranquilizer) are the official drugs included in Model List of Essential Drugs of World Health Organization (WHO). Therefore, we have attempt to identify and characterize the MIAs in the crude extracts of six Rauwolfia species using ultrahigh-performance liquid chromatography coupled with Orbitrap Velos Pro hybrid mass spectrometer. The identity of the MIAs were construed using the high resolution tandem mass spectrometry (HRMS/MS) spectra of standard compounds 'yohimbine' and 'reserpine' in higher energy collisional dissociation (HCD) and collision-induced dissociation (CID) modes. The diagnostic fragment ions found in HCD mode was highly affected by variation of normalized collision energy (NCE) and gave few product ions ('C-F') while CID produced intense and more diagnostic product ions ('A-F'). Consequently, CID-MS/MS mode provided significantly more structural information about basic skeleton and therefore the recommended mode for analysis of MIAs. Furthermore, six diagnostic fragmentation pathways were established by multi-stage mass analysis (MS(n) (n=5)) analysis which gave information regarding the substitution. Fragment ions 'A-F' revealed the number and position of substituents on indole and terpene moieties. The proposed diagnostic fragmentation pathways have been successfully applied for identification and characterization of MIAs in crude root extracts of six Rauwolfia species. Ten bioactive reserpine class of MIAs were tentatively identified and characterized on the basis of chromatographic and mass spectrometric features as well as HRMS/MS an MS(n) (n=4) analysis. PMID:26551537

  3. The effects of release and depletion of endogenous noradrenaline on the transmission of impulses in the mouse vas deferens

    PubMed Central

    Marshall, I.; Nasmyth, P.A.; Shepperson, N.B.

    1978-01-01

    1 The effects of endogenous noradrenaline released by tyramine and the influence of depletion of the tissue noradrenaline with reserpine and/or α-methyl-p-tyrosine on the twitch responses of the field-stimulated mouse vas deferens have been studied. 2 Tyramine (10-40 μM) inhibited the twitch responses to field stimulation and failed to produce a contraction. The inhibition decreased as the rate of stimulation increased. 3 The inhibition produced by tyramine was antagonized by cocaine (10 μM) and by yohimbine (10 nM), which indicated that it was produced by released noradrenaline acting on presynaptic α-adrenoceptors. 4 Depletion of the tissue noradrenaline by 39% by blockade of the synthesis of noradrenaline with α-methyl-p-tyrosine, was without effect on the twitch response but it reduced the inhibitory effect of tyramine. 5 Depletion of the tissue noradrenaline by 96.5% with reserpine alone and by 99.4%, with a combination of reserpine and α-methyl-p-tyrosine, reduced the twitch responses by approximately 66% and virtually abolished the inhibition produced by tyramine. It also increased the rate of decline of the responses when the tissue was continuously stimulated. The remaining twitch was not antagonized by phenoxybenzamine (15 μM). 6 Residual twitches were bigger in tissues depleted by 99.4% than in those depleted by only 96.5%. This difference was eliminated in the presence of yohimbine (128 nM). 7 It is concluded that inhibition of the twitch responses by tyramine is produced by stimulation of presynaptic α-adrenoceptors and that the twitch response is associated with stimulation of the sympathetic neurone, but that it is not mediated by postsynaptic α-adrenoceptors. PMID:212149

  4. Photosensitizer-induced fluorescence of the rat adrenal gland and rat pheochromocytoma cells (PC 12) by meso-tetra(hydroxyphenyl)chlorin (mTHPC)

    NASA Astrophysics Data System (ADS)

    Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Heym, Christine; Senninger, Norbert

    1997-12-01

    Rat adrenal glands exhibit an intense mTHPC-induced fluorescence. The objective of our study was the identification of adrenal cells exhibiting mTHPC-induced fluorescence under normal conditions and under stimulation of adrenal proliferation by reserpine. Furthermore mTHPC-uptake of rat pheochromocytoma (PC 12) cells was investigated. Four male Wistar rats received 0.5 mg mTHPC/kg iv 48 hours before perfusion. Furthermore four rats received reserpine (2 mg/kg im od), bromo-deoxy-uridine (BrdU; 50 mg/kg ip od) each for one week and mTHPC (0.5 mg/kg) 48 hours before perfusion. BrdU was detected immunohistochemically. PC 12-cells were incubated with 0.5 mg mTHPC/l culture medium for 24 or 48 hours. Cells and tissues were examined by fluorescence microscopy. The adrenal cortex exhibited an intense mTHPC-induced fluorescence. The adrenal medulla fluoresced faintly. Reserpine increased fluorescence of intramedullary cells, not coinciding with adrenal proliferation. Cortical fluorescence remained unchanged. PC 12-cells lying singly or in small groups and differentiating cells showed a more intense mTHPC- induced fluorescence than confluent cells. Differences of cortical and medullary uptake of mTHPC are independent of proliferation and may be explained by lipophilia of mTHPC, since adrenocytes have an uptake mechanism for cholesterol. The difference of mTHPC-uptake between PC 12-cells and chromaffin cells implicate the possibility of photodynamic applications for medullary neoplasia.

  5. Sympathetic outflow activates the venom gland of the snake Bothrops jararaca by regulating the activation of transcription factors and the synthesis of venom gland proteins.

    PubMed

    Luna, Milene S A; Hortencio, Thiago M A; Ferreira, Zulma S; Yamanouye, Norma

    2009-05-01

    The venom gland of viperid snakes has a central lumen where the venom produced by secretory cells is stored. When the venom is lost from the gland, the secretory cells are activated and new venom is produced. The production of new venom is triggered by the action of noradrenaline on both alpha(1)- and beta-adrenoceptors in the venom gland. In this study, we show that venom removal leads to the activation of transcription factors NFkappaB and AP-1 in the venom gland. In dispersed secretory cells, noradrenaline activated both NFkappaB and AP-1. Activation of NFkappaB and AP-1 depended on phospholipase C and protein kinase A. Activation of NFkappaB also depended on protein kinase C. Isoprenaline activated both NFkappaB and AP-1, and phenylephrine activated NFkappaB and later AP-1. We also show that the protein composition of the venom gland changes during the venom production cycle. Striking changes occurred 4 and 7 days after venom removal in female and male snakes, respectively. Reserpine blocks this change, and the administration of alpha(1)- and beta-adrenoceptor agonists to reserpine-treated snakes largely restores the protein composition of the venom gland. However, the protein composition of the venom from reserpinized snakes treated with alpha(1)- or beta-adrenoceptor agonists appears normal, judging from SDS-PAGE electrophoresis. A sexual dimorphism in activating transcription factors and activating venom gland was observed. Our data suggest that the release of noradrenaline after biting is necessary to activate the venom gland by regulating the activation of transcription factors and consequently regulating the synthesis of proteins in the venom gland for venom production. PMID:19411547

  6. Spectrophotometric determination of hydralazine with 2-hydroxy-1-naphthaldehyde in pharmaceuticals.

    PubMed

    Mari-Buigues, J; Mañes-Vinuesa, J; Garcia-Domenech, R; Pous-Miralles, G

    1991-07-01

    A new extraction-spectrophotometric method for the determination of hydralazine, based on its reaction with 2-hydroxy-1-naphthaldehyde at 25 degrees C, is described. The calibration curve was linear between 0.4 and 6 mg/mL of hydralazine. The molar absorbtivity of the product at 408 nm is 40,900 L.mol-1.cm-1. The method described was applied to the analysis of hydralazine in pharmaceutical preparations containing reserpine, hydrochlorothiazide, bendrofluorthiazine, propranolol, and other substances. The agreement with the U.S.P. XXI method was satisfactory for tablets and injections, but not for pellets. PMID:1941570

  7. [Investigation of the effect of efflux pump inhibitors to MIC values of ciprofloxacin in clinical isolates of Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus].

    PubMed

    Cetinkaya, Ebru; Coban, Ahmet Yilmaz; Durupinar, Belma

    2008-10-01

    The aim of this study was to investigate the effects of efflux pump inhibitors on the minimal inhibitory concentration (MIC) values of ciprofloxacin (CIP) in fluoroquinolone-resistant 42 Pseudomonas aeruginosa (n= 42), Escherichia coil (n= 97), Acinetobacter baumannii (n= 58) and Staphylococcus aureus (n= 80) strains isolated from clinical specimens. For this purpose phenylalanyl-arginyl-beta-naphthylamide (PA beta N) was used for P. aeruginosa, E. coli, A. baumannii and reserpine for S. aureus isolates as pump inhibitors. Fluoroquinolone resistance of the clinical isolates were determined by VITEK2 Compact (BioMerieux, France) automated system and confirmed with standard broth microdilution method. For the investigation of the effects of inhibitor agents, the MIC values were also determined in the presence of 25 microg/ml and 100 microg/ml PA beta N and 20 microg/ml reserpine. In the presence of 25 mg/l PA beta N, 61.9% of CIP resistant P. aeruginosa strains converted to susceptible ones, while this rate was 73.8% in the presence of 100 mg/l PA beta N. In A. baumannii clinical isolates, 8.6% and 15.5% of CIP-resistant strains have become susceptible in the presence of 25 mg/l and 100 mg/l PA beta N, respectively. Similarly the MIC values for CIP have decreased > or = 4 folds in 42.2%, and > or = 2 folds in 30.9% of E. coli isolates, in the presence of 25 mg/l PA beta N, however, there was no change in MICs of 26.9% of E. coli strains. The MIC values have also been lowered for > or = 4 folds in 83.6%, and two folds in 13.4% of E. coli strains by the use of 100 mg/l PA beta N concentration, however, no decrease in MIC values was detected in 3% of the isolates. 20 mg/l of reserpine have caused a decrease of > or = 4 folds in 8.75%, and two folds in 33.75% of S. aureus isolates, while there was no change in MIC values of 57.5% of S. aureus strains. Our results showed that PA beta N causes significant reduction in MIC values for CIP in the clinical isolates of P

  8. Amphetamine-enhanced accumulation of ( sup 3 H)-spiperone in mouse corpus striatum in vivo: Modification by other drugs

    SciTech Connect

    Dorris, R.L. )

    1989-01-01

    Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with ({sup 3}H)-spiperone (20 {mu}Ci/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before ({sup 3}H)-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by {alpha} - methyltyrosine ({alpha}-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of ({sup 3}H)-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by {alpha}-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release.

  9. Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats

    SciTech Connect

    Tariq, M.; Parmar, N.S.; Ageel, A.M.

    1987-05-01

    Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

  10. Monoamine mediation of the morphine-induced activation of mice

    PubMed Central

    Carroll, Bernard J.; Sharp, Peter T.

    1972-01-01

    1. The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2. The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3. The monoamine precursors L-DOPA and 5-hydroxytryptophan potentiate the response. 4. The monoamine synthesis inhibitors α-methyl-p-tyrosine and p-chlorophenylalanine reduce the response. 5. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7. Blockade of α-adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10. The tricyclic antidepressant drug imipramine potentiated the response. 11. The morphine antagonist nalorphine completely prevented the response. 12. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13. We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance. PMID:4263794

  11. Central action of phenylethylamine in rats.

    PubMed

    Jagiełło-Wójtowicz, E

    1981-01-01

    Phenylethylamine (PEA), 10, 50 and 100 microgram/rat ivc depressed the spontaneous and explorative motor activities, did not affect the body temperature and potentiated the action of hypnotics. The PEA-induced depression of motor activity was antagonized by spiperone, phenoxybenzamine, propranolol and, slightly, by alpha-MT. In rats with total chemical destruction of catecholamine neurons and in rats with selective lesion of dopamine neurons, PEA increased motor activity. Similar effect was observed after administration of reserpine, reserpine together with 6-hydroxydopamine and yohimbine. PEA potentiated the amphetamine and apomorphine stereotypy but inhibited amphetamine hypermotility: in the latter experiment slight periodical stereotyped head movements were observed. PEA did not affect haloperidol and fluphenazine induced catalepsy. It did not change the immobility period in the behavioral despair test. In doses of 0 . 1, 1 and 10 mg/kg iv it potentiated flexor reflex of the hind paw of the spinal rat. Phentolamine (10 mg/kg iv) and propranolol (5 mg/kg iv) slightly potentiated the stimulatory effect of PEA. In doses of 50 and 100 microgram ivc PEA did not affect the level and utilization of noradrenaline, and did not change the level of dopamine but depressed its utilization in the cerebral cortex, striatum and hippocampus. PMID:7196039

  12. Involvement of the central monoaminergic system in the antidepressant-like effect of catalpol in mice.

    PubMed

    Wang, Junming; Cui, Ying; Feng, Weisheng; Zhang, Yueyue; Wang, Guifang; Wang, Xingxing; Zhou, Gai

    2014-10-01

    Catalpol is a natural iridoid glycoside with diverse bioactivities that is found in abundance in Rehmannia glutinosa Libosch. (Scrophulariaceae). The present study assessed whether catalpol treatment (5, 10, or 20 mg/kg for 14 days by intragastric administration (i.g.)) has an antidepressant-like effect on mice performing the forced swim test (FST), tail suspension test (TST), open field test (OFT), and tests for reversal of reserpine-induced ptosis, akinesia, and hypothermia. This study also examined the potential role that catalpol plays in the cerebral monoaminergic system. Results indicated that catalpol administration produced an antidepressant-like effect in mice, as indicated by the reduced duration of immobility in the FST and TST, but it had no effect on locomotor activity in the OFT. Catalpol treatment significantly counteracted the decrease in rectal temperature, akinesia, and eyelid ptosis induced by reserpine. Moreover, catalpol increased levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brains of mice, but it did not affect levels of norepinephrine (NE) or dopamine (DA). These antidepressant-like effects of catalpol are essentially similar to the effects of the clinical antidepressant fluoxetine hydrochloride (FH). This is the first study to indicate that catalpol has an antidepressant-like effect and that its action may be mediated by the central serotonergic system, and not by noradrenergic or dopaminergic systems. PMID:25382440

  13. alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals.

    PubMed

    Donoso, M Veronica; Carvajal, Andrés; Paredes, Alfonso; Tomic, Alexander; Koenig, Cecilia S; Huidobro-Toro, J Pablo

    2002-09-01

    Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms. PMID:12217427

  14. Drug-induced regulation of 1,4-dihydropyridine Ca sup 2+ channel antagonist binding sites in the brain and heart

    SciTech Connect

    Ramkumar, V.

    1987-01-01

    The ability of drugs to regulate the voltage-sensitive Ca{sup 2+} channels were assessed by determining the bind of ({sup 3}H)dihydropyridine Ca{sup 2+} channel antagonists in the heart and brain following administration of these drugs to rats and mice. Mice and rats implanted with morphine pellets for 3 days showed an increase in dihydropyridine binding sites in the brain, compared to non-treated or placebo treated controls. No increase in dihydropyridine binding sites was observed in the heart. The significance of the increase in binding to physical dependence on morphine is implied from the findings that pretreatment with Ca{sup 2+} channel antagonist drugs led to an attenuation of naloxone-precipitated withdrawal signs in both dependent rats and mice. Administration of other drugs, known to depress the CNS, was undertaken to determine whether the changes observed with morphine was a nonspecific response of the brain to depressant drugs. Prolonged administration of reserpine to rats resulted in no changes in dihydropyridine binding sites in the brain, even though the {beta}-adrenergic receptors in this tissue are upregulated. However, reserpine decreased the density of ({sup 3}H)nimodipine binding sites in the heart of this is accompanied by concomitant increases in {beta}-adrenergic receptors.

  15. Coadministration of Resveratrol and Rice Oil Mitigates Nociception and Oxidative State in a Mouse Fibromyalgia-Like Model

    PubMed Central

    Peres Klein, Caroline; Rodrigues Cintra, Marcos; Binda, Nancy; Montijo Diniz, Danuza; Gomez, Marcus Vinicius; Souto, Andre Arigony; de Souza, Alessandra Hubner

    2016-01-01

    The mechanism underlying pain symptoms in fibromyalgia (FM) is not fully understood. Oxidative stress has emerged as pathophysiological event occurring during the development of the disease. The present study aimed at investigating the efficacy of resveratrol associated with rice bran oil on fibromyalgia-like mice model. Subcutaneous injection of reserpine (0.25 mg/Kg) during 3 days produced fibromyalgia-like symptoms. Resveratrol and/or rice oil or pregabalin were administered through oral route in therapeutic (single dose) and preventive (four doses) schemes. In both schemes, treatment with resveratrol associated with rice bran oil and pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia in animals. The preventive scheme displayed antidepressant effect which was demonstrated by the forced swimming test as well as reduced reactive species in the cerebrospinal fluid of reserpinized animals. Taken together, our data provide evidences that the intake of resveratrol associated with rice bran oil plays antinociceptive and antidepressant actions probably through reducing reactive species and suggests the involvement of oxidative stress in this model of FM as possible underlying mechanism of pathogenesis of the disease. PMID:27069683

  16. Effect of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on killing Acinetobacter baumannii by colistin.

    PubMed

    Park, Young Kyoung; Ko, Kwan Soo

    2015-01-01

    We investigated the effect of cyanide 3-chlorophenylhydrazone (CCCP) and other efflux pump inhibitors (EPIs) on the colistin susceptibility in Acinetobacter baumannii. While minimum inhibitory concentrations (MICs) of colistin in all colistin-resistant strains decreased significantly with 25 μM of CCCP and 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not decrease the colistin MICs. However, CCCP and DNP as well as PAβN and reserpine did not have a significant effect on the MICs of the other agents. Efflux pump gene expressions in colistin-resistant strains were not increased compared with those in colistin-susceptible strains. When only 5X MIC of colistin (5 mg/L) was provided to a colistin-susceptible A. baumannii strain, the bacterial cell number was reduced by 9 h after exposure to colistin, but regrowth was observed. When CCCP was added to colistin, bacterial cells were completely killed after 24 to 48 h of incubation, which was not due to the toxicity of CCCP itself. Colistin resistance in A. baumannii may not be due to efflux pumps. Our present study suggests that bacterial cells with reduced metabolic activity by CCCP are more susceptible to colistin in A. baumannii. It may show the possibility that combined therapy with colistin and other antimicrobial agents could effective against A. baumannii infections. PMID:25557480

  17. Multiwalled Carbon Nanotubes-Dispersive Solid-Phase Extraction Coupled with UPLC-ESI-MS-MS for Simultaneous Determination of 10 Illegal Adulterants in Antihypertensive Functional Foods.

    PubMed

    Hu, Jielan; Zeng, Li; He, Ling; You, Fan; Sun, Chengjun

    2016-05-01

    A reliable method for simultaneous determination of 10 illegal adulterants including chlortalidone, hydrochlorothiazide, indapamide, metoprolol, nifedipine, nimodipine, nitrendipine, reserpine, triamterene and valsartan in antihypertensive functional foods by ultra-high-performance liquid chromatography coupled with electrospray ionization-tandem mass spectrometry is presented in this article. The target chemicals were extracted with acetonitrile ultrasonically and cleaned up using multiwalled carbon nanotubes-dispersive solid-phase extraction. The separation was performed on a Waters ACQUITY UPLC BEH C18 Column (2.1 × 100 mm, 1.7 µm) with acetonitrile, 0.1% formic acid and 10 mmol/L ammonium acetate solution as mobile phase at a flow rate of 0.2 mL/min. Multiple reaction monitoring was applied for detection and sildenafil was used as the internal standard. The correlation coefficients of the method were >0.995, with the limits of detection of 0.022-0.30 ng/mL and the limits of quantification of 0.075-0.99 ng/mL. The interday and intraday relative standard deviations were <9.77% and the recoveries were in the range of 85.8-109%. The established method has been applied for the analysis of real samples, and reserpine was detected in a tonic wine sample with a content of 60.1 ± 3.2 mg/L. PMID:26850731

  18. 7-(3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy)-2 (1H)-quinolinone (OPC-4392), a presynaptic dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist

    SciTech Connect

    Yasuda, Y.; Kikuchi, T.; Suzuki, S.; Tsutsui, M.; Yamada, K.; Hiyama, T.

    1988-01-01

    The assertion that OPC-4392 acts as an agonist at presynaptic dopamine autoreceptors is supported by the following behavioral and biochemical observations: OPC-4392, 3-PPP and apomorphine inhibited the reserpine-induced increase in DOPA accumulation in the forebrain of mice and in the frontal cortex, limbic forebrain and striatum of rats. In addition, the gamma-butyrolactone (GBL)-induced increase in DOPA accumulation in the mouse forebrain was also inhibited by OPC-4392, 3-PPP and apomorphine. The inhibitory effect of OPC-4392 on GBL-induced DOPA accumulation lasted for at least 8 hours after oral administration to mice, while that of 3-PPP and apomorphine disappeared in 4 hours after subcutaneous injection. OPC-4392 failed to increase spontaneous motor activity in reserpinized mice, enhance spontaneous ipsilateral rotation in rats with unilateral striatal kainic acid (KA) lesions, induce contralateral rotation in rats with unilateral striatal 6-hydroxydopamine (6-OHDA) lesions and inhibit /sup 14/C-acetylcholine (Ach) release stimulated by 20 mM KCl in rat striatal slices.

  19. Evidence for participation of catecholamines in cardiac action of ouabain

    PubMed Central

    Seifen, E.

    1974-01-01

    1 The shortening of cycle length (=positive chronotropic effect) by ouabain produced in isolated spontaneously beating atria of the guinea-pig was analyzed. 2 The action of ouabain was dose-dependent; threshold response was seen at 1 × 10-7 M, and maximal response occurred at 4 × 10-7 M. The half-time of the ouabain effect was about 20 minutes. 3 The positive chronotropic effect of ouabain was reduced to 40% by β-adrenoceptor blockade (3.3 × 10-9 M propranolol) or by reserpine-depletion of catecholamines. Incubation of reserpine-treated atria with noradrenaline partially restored the action of ouabain. 4 The effect of ouabain was greatly dependent upon the calcium concentration. The optimal calcium level was 2.5 × 10-3 M. Calcium and ouabain acted synergistically. 5 Increasing calcium concentrations inhibited the positive chronotropic effect of noradrenaline in a manner similar to increasing ouabain concentrations. 6 A hypothesis is proposed which explains the chronotropic effect of ouabain on the basis of two mechanisms: (1) increase of the catecholamine concentration affecting the pacemaker; (2) mobilization of calcium, i.e. increase of the biologically effective intracellular calcium level. PMID:4451762

  20. Effects of acute catecholamine depletion on cardiac function in normotensive and spontaneously hypertensive rats

    SciTech Connect

    Sellke, F.; Sadri, F.; Ely, D.

    1986-03-01

    Reserpine(6mg/Kg) was injected IP in Wistar (n = 5, age 10 wks.) and spontaneously hypertensive (SHR) rats (n = 5, age 16 wks.). After 4 hours the hearts were isolated (Langendorff), perfused with Krebs-Henseleit solution and paced at 240/min. Non-injected Wistar (N = 5) and SHR (n = 6) rats were used for controls. Myocardial levels of norepinephrine (NE) and epinephrine (E) were determined with radioenzymatic assay. Left ventricular systolic and distolic pressures were recorded for left ventricular end diastolic volumes (LVEDV) .05 to .40 ml. Despite a marked decrease in tissue levels of NE and E, peak systolic pressure (PSP) increased in reserpine treated normotensive and SHR rats. In isolated control SHR rat hearts (LVEDV = .20 ml), PSP was related to NE by PSP = .0145 (NE) + 93 (r = .819, p < .01). In conclusion, cardiac performance and tissue levels of myocardial catecholamines are correlated in control rats. However, rapid depletion of myocardial catecholamines may result in increased cardiac performance.

  1. An investigation of the tachycardia produced by intracerebro-ventricular injections of isoprenaline in mice.

    PubMed Central

    Burden, D T; Parkes, M W

    1975-01-01

    1. Isoprenaline, 3.5-20 ng, injected intracerebroventricularly in atropinized mice under pentobarbitone anaesthesia produced a dose-dependent tachycardia. 2. Pretreatment with either reserpine or pempidine blocked nervously-mediated tachycardia as shown by marked reduction of that due to stimulation of the spinal outflow in pithed mice. After pretreatment with these drugs, intracerebroventricular isoprenaline caused tachycardia of a similar degree and time course to that in mice not so pretreated. 3. Pretreatment with either reserpine or pempidine caused supersensitivity to the tachycardia due to intravenous isoprenaline. 4. When allowance was made for this supersensitivity in the effect of intracerebroventricular isoprenaline in pretreated mice, a small dose-dependent residual effect remained that could be attributed to leakage of isoprenaline into the peripheral circulation. 5. This was confirmed by the appearance of a late-developing tachycardia on intracerebroventricular injection of isoprenaline in spinal mice. 6. It is therefore concluded that the tachycardia caused by intracerebroventricular isoprenaline in mice is, at least initially, of central origin. PMID:1137728

  2. Dopamine Disposition in the Presynaptic Process Regulates the Severity of Methamphetamine-induced Neurotoxicity

    PubMed Central

    KUHN, DONALD M.; FRANCESCUTTI-VERBEEM, DINA M.; THOMAS, DAVID M.

    2008-01-01

    Methamphetamine (METH) is well-known for its ability to cause damage to dopamine (DA) nerve endings of the striatum. The mechanisms by which METH causes neurotoxicity are not fully understood but likely candidates are increased oxidative and nitrosative stress and mitochondrial dysfunction. Microglial activation is also emerging as an important element of the METH neurotoxic cascade and it appears that extensive crosstalk between these cells and DA nerve endings is an early event in this process. It may seem paradoxical, but DA itself is also thought to be an essential factor in the neuronal damaging effects of METH, but issues relating to its precise role in this regard remain unanswered. We present in this overview a summary of studies that tested how alterations in the disposition of presynaptic DA (injections of reserpine, L-DOPA, or clorgyline) modulate METH neurotoxicity. In all cases, these drugs significantly increased the magnitude of microglial activation as well as the severity of damage to striatal DA nerve endings caused by METH. The enhancement of METH effects in striatum by reserpine, L-DOPA, and clorgyline persisted for 14 days and showed no evidence of recovery. These data establish that subtle shifts in the newly-synthesized pool of DA can cause substantial changes in the severity of METH-induced neurotoxicity. DA released into the synapse by METH is very likely the source of downstream reactants that provoke microglial activation and the ensuing damage to DA nerve endings. PMID:18991856

  3. Beneficial Effects of Maprotiline in a Murine Model of Colitis in Normal and Reserpinised Depressed Rats

    PubMed Central

    Minaiyan, Mohsen; Hajhashemi, Valiollah; Rabbani, Mohammad; Fattahian, Ehsan; Mahzouni, Parvin

    2014-01-01

    Background. Anti-inflammatory and immunomodulatory activities have been reported for maprotiline, a strong norepinephrine reuptake inhibitor. In addition, some other antidepressant drugs have shown beneficial effects in experimental colitis. Methods. All the animals were divided into normal and depressed groups. In normal rats colitis was induced by instillation of 2 mL of 4% acetic acid and after 2 hours, maprotiline (10, 20, and 40 mg/kg, i.p.) was administered. In reserpinised depressed rats, depression was induced by injection of reserpine (6 mg/kg, i.p.), 1 h prior to colitis induction, and then treated with maprotiline (10, 20, and 40 mg/kg). Treatment continued daily for four days. Dexamethasone (1 mg/kg, i.p.) was given as a reference drug. On day five following colitis induction, animals were euthanized and distal colons were assessed macroscopically, histologically, and biochemically (assessment of myeloperoxidase activity). Results. Maprotiline significantly improved macroscopic and histologic scores and diminished myeloperoxidase activity in both normal and depressed rats while reserpine exacerbated the colonic damage. Conclusion. Our data suggests that the salutary effects of maprotiline on acetic acid colitis are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug. PMID:27355055

  4. Norepinephrine storage, distribution, and release in diabetic cardiomyopathy

    SciTech Connect

    Ganguly, P.K.; Beamish, R.E.; Dhalla, K.S.; Innes, J.R.; Dhalla, N.S.

    1987-06-01

    The ability of hearts to store, distribute, and release norepinephrine (NE) was investigated in rats 8 wk after the induction of diabetes by an injection of streptozotocin. Chronic diabetes was associated with increased content and concentration of NE in heart and in other tissues such as kidney, brain, and spleen. Reserpine or tyramine treatment resulted in depletion of endogenous cardiac NE in control and diabetic rats. The depletion of NE stores at different times after a dose of reserpine was greater in diabetic hearts. On the other hand, NE stores in diabetic hearts were less sensitive than control hearts to low doses of tyramine but were more sensitive to high doses. The uptake of (/sup 3/H)NE was greater in diabetic hearts in isolated perfused preparations. In comparison with the control values, diabetic hearts showed a decrease in (/sup 3/H)NE in the granular fraction and an increase in the supernatant fraction. Diabetic hearts also showed an accelerated spontaneous release of (/sup 3/H)NE. The increased cardiac NE and the uptake and release of NE in diabetic animals were reversible upon treatment with insulin. These results are consistent with the view that sympathetic activity is increased in diabetic cardiomyopathy and indicate that cardiac NE in diabetic rats is maintained at a higher level partly due to an increased uptake of released NE by adrenergic nerve terminals.

  5. Cisplatin-induced early and delayed emesis in the pigeon

    PubMed Central

    Tanihata, Sachiko; Igarashi, Hiroaki; Suzuki, Masami; Uchiyama, Toshimitsu

    2000-01-01

    Intravenously injected cisplatin at a dose of 4 mg kg−1 induced early and delayed emesis in all pigeons without occurrence of lethality during a 72 h observation period. The early emetic response occurred with a latency of 81.3±8.0 min (n=15) and reached a peak at 2–3 h, and decreased gradually within 8 h after injection. Then the delayed emetic response, whose peak was found between 10 to 23 h, lasted up to 48 h. The emetic response markedly declined after 48 h.Reserpine markedly reduced monoamine levels in both brain and intestine and completely abolished the early and delayed emesis. Dexamethasone markedly reduced not only the early but also the delayed emetic responses. p-Chlorophenylalanine decreased the level of serotonin in brain and intestine without affecting noradrenaline and dopamine and partly reduced the early emetic response, but did not affect delayed emesis.Bilateral vagotomy prolonged the latency time to the onset of early emesis, and reduced the emetic responses in both the early and delayed phases.The above results suggest that the cisplatin-induced early emesis in the pigeon is partially mediated via the vagal nerve and reserpine-sensitive monoaminergic systems including the serotonergic system; the delayed emesis is associated with monoaminergic but not the serotonergic systems. PMID:10781008

  6. Coadministration of Resveratrol and Rice Oil Mitigates Nociception and Oxidative State in a Mouse Fibromyalgia-Like Model.

    PubMed

    Peres Klein, Caroline; Rodrigues Cintra, Marcos; Binda, Nancy; Montijo Diniz, Danuza; Gomez, Marcus Vinicius; Souto, Andre Arigony; de Souza, Alessandra Hubner

    2016-01-01

    The mechanism underlying pain symptoms in fibromyalgia (FM) is not fully understood. Oxidative stress has emerged as pathophysiological event occurring during the development of the disease. The present study aimed at investigating the efficacy of resveratrol associated with rice bran oil on fibromyalgia-like mice model. Subcutaneous injection of reserpine (0.25 mg/Kg) during 3 days produced fibromyalgia-like symptoms. Resveratrol and/or rice oil or pregabalin were administered through oral route in therapeutic (single dose) and preventive (four doses) schemes. In both schemes, treatment with resveratrol associated with rice bran oil and pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia in animals. The preventive scheme displayed antidepressant effect which was demonstrated by the forced swimming test as well as reduced reactive species in the cerebrospinal fluid of reserpinized animals. Taken together, our data provide evidences that the intake of resveratrol associated with rice bran oil plays antinociceptive and antidepressant actions probably through reducing reactive species and suggests the involvement of oxidative stress in this model of FM as possible underlying mechanism of pathogenesis of the disease. PMID:27069683

  7. Covalent modification of the amine transporter with N,N prime -dicyclohexylcarbodiimide

    SciTech Connect

    Suchi, R.; Stern-Bach, Y.; Gabay, T.; Schuldiner, S. )

    1991-07-02

    N,N{prime}-Dicyclohexylcarbodiimide (DCC) has been previously shown to inhibit the amine transporter from chromaffin granules. A study of the mechanism of inhibition is present together with the demonstration of covalent modification of the protein. DCC inhibits binding of R1 (reserpine) and R2 (tetrabenazine) types of ligands to the transporter as well as transport. Lignads of the R2 type, but not those of the R1 type, protect against inhibition of all the reactions by DCC, i.e., accumulation of serotonin, binding if reserpine (R1 ligand), and binding of ketanserine (R2 ligand). The ability of a given R2 ligand to protect the transporter correlates well with its binding constant. Water-soluble carbodiimides, such as 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide (EDC), do not have any effect on the catalytic activity of the transporter. A flourescent hydrophobic analogue of DCC, N-cyclohexyl-N{prime}-(4-(dimethylamino)-{alpha}-naphthyl)carbodiimide (NCD-4), inhibits at about the same concentration range as DCC. ({sup 14}C)DCC labels several polypeptides in the chromaffin granule membranes. Labeling of a polypeptide with an apparent M{sub r} of 80K is inhibited in the presence of R2 ligands. The labeled polypeptide copurifies with the recently identified and isolated transporter.

  8. Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation.

    PubMed

    Shreevathsa, M; Ravishankar, B; Dwivedi, Rambabu

    2013-01-01

    Depression is a psychiatric condition in which there is loss of interest in all pleasurable outlets, viz. food, sex, work, friends, hobbies and entertainment. The prevalence rate of the disease is 6-8% in women and 3-5% in men. Ayurveda, the science of life, provides systematic management principles for depression. Mamsyadi Kwatha is one such formulation stated by Yadavji Trikamji Acharya in Siddha Yoga Sangraha and Bheshaja Samhita, which is said to be effective in psychiatric conditions. The ingredients are Jatamansi (Nardostachys jatamansi), Ashwagandh (Withania somnifera) and Parasika Yavani (Hyocymus niger) in an 8:4:1 ratio, respectively. The test drug was subjected for antidepressant activity in experimental models. The models selected for anti depressant activity were behavioral despair test, anti-reserpine test and Chronic Fatigue Syndrome (CFS) test in albino mice. The test formulation showed significant inhibition of behavioural despair (P < 0.05), weak to moderate anti-reserpine activity - ptosis (P < 0.001), catatonia (P < 0.01), sedation (P < 0.01) and moderate effect in CFS test (P < 0.050). These effects clearly show that Mamsyadi Kwatha has an anti-depressant activity. PMID:24049416

  9. Circadian rhythm of alpha-amylase in rat parotid gland.

    PubMed

    Bellavía, S L; Sanz, E G; Chiarenza, A P; Sereno, R; Vermouth, N T

    1990-01-01

    The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general. PMID:2076161

  10. Biochemical and physiological effects of chlordimeform.

    PubMed Central

    Matsumura, F; Beeman, R W

    1976-01-01

    Chlordimeform is a relatively new acaricide/insecticide, whose mode of action we have investigated. It appears to interfere with amine-mediated control of nervous and endocrine systems in a variety of ways. Specifically, chlordimeform causes a build-up of the amines 5-hydroxytryptamine and to a lesser extent norepinephrine in the rat brain in vivo, antagonizes the in vivo action of reserpine in the rat (reserpine depletes amine stores in the CNS), inhibits monoamine oxidase from rat liver in vitro, and causes hypotension in rabbits. In the American cockroach it directly stimulates the heart in situ, acts synergistically with tryptamine in vivo, inhibits amine-N-acetyltransferase from cockroach head in vitro, causes accumulation of indolamines in cockroaches in vivo, and blocks the stimulation of adenylate cyclase by octopamine in the cockroach CNS in situ. It also inhibits tryptamine metabolism in whole mites in vitro. Images FIGURE 3. FIGURE 4. A FIGURE 4. B FIGURE 4. C FIGURE 4. D PMID:976227

  11. [Induction of lactation in cattle after short-term hormonal treatment].

    PubMed

    Manunta, G; Naitana, S

    1981-01-30

    In wintertime 7 nonpregnant cows (3 nonlactating and 4 milk secreting less than 3 liter/day) and 3 heifers were treated:day 1 cloprostenol (530 microgram); day 2 progesterone capronate (0,25/Kg); days 3 to 5 progesterone (0,25 mg/Kg)+ estradiol valerianate (0,01 mg/Kg) and reserpine (0,01 mg/Kg); days 6 to 8 progesterone (0,25 mg/Kg) + estradiol (0,2 mg/Kg) and reserpine (0,01 mg/Kg); day 9 betametasone acetate (0,2 mg/Kg) and phosphate (0,55 mg/Kg); days 9 to 16 estradiol (0,0075 mg/Kg). 9 days later the treatment started again. In all the period (5/12-25/2) the animals where machine milked. 2 lactating nonpregnant cows where kept as control. The milk secretion started in nonlactating animals but the peak daily milk yield was 3 liter about only. In lactating animals the yield no increased. The second treatment (and the first in lactating cows) induced secreting less milk with more fat and protein. The low milk yields was associated to a season's negative effect. PMID:6786306

  12. Mechanism of cardiovascular actions of heptanolamines

    PubMed Central

    Garrett, J.; Osswald, W.; Moreira, M. Gonçalves

    1962-01-01

    It has been suggested that heptaminol and methylheptaminol should be used as myocardial stimulants because they have cardiotonic actions similar to those of cardiac glycosides. However, as these aliphatic amines show definite sympathomimetic effects, the mechanism of their actions on the heart was investigated, in order to determine whether digitalis-like properties are involved in these effects. The pattern of pharmacological actions of heptaminol and methylheptaminol was compared with that of catechol amines, tyramine and k-strophanthin. The influence of atropine, hexamethonium, cocaine and reserpine was also investigated. The results show that both heptanolamines have a long-lasting cardiostimulant action which is abolished by cocaine and absent in reserpine pretreated animals. The pharmacological activity of these drugs may be entirely attributed to an indirect sympathomimetic action of the tyramine type, probably due to release of endogenous catechol amines. None of the experimental findings is consistent with the alleged digitalis-like action of these compounds. ImagesFig. 5Fig. 6 PMID:13897064

  13. The medical treatment of Parkinson disease from James Parkinson to George Cotzias.

    PubMed

    Fahn, Stanley

    2015-01-01

    It took exactly 150 years since James Parkinson's description in 1817 of the illness bearing his name until the development of effective therapy for this disorder, namely, the introduction of high-dosage levodopa by George Cotzias in 1967. During the first 50 years, no effective therapy was available, but neurologists reported using different agents, including metals. Then, around 1867, Charcot found solanaceous alkaloids to be somewhat helpful, and these became the accepted and popular therapy for the next 75 years. When basic scientists discovered that these alkaloids had central antimuscarinic activity, pharmaceutical chemists developed synthetic chemical agents that were equally effective, with possibly less adverse effects, and around 1950 these synthetic drugs became the standard medical therapy for Parkinson's disease (PD). The link between dopamine and PD did not take place until 1957, 140 years after Parkinson's Essay. The clue came from research on reserpine, a drug derived from the Rauwolfia plant that caused a sedative effect, now recognized as a drug-induced parkinsonian state. Initial investigations revealed that reserpine caused the release and depletion of serotonin stores in the brain. With that knowledge, Arvid Carlsson, a young pharmacologist in Sweden, decided to explore the possibility that reserpine might also affect brain catecholamines. In his now famous, elegant, and simple experiment, he showed that injecting l-dopa, the precursor of catecholamines, alleviated the reserpine-induced parkinsonian state in animals, whereas the precursor of serotonin failed to do so. Carlsson then developed a highly sensitive assay to measure dopamine, and his lab found that dopamine is selectively present in high concentrations in the striatum and that administered l-dopa could restore the dopamine depleted by reserpine. Carlsson postulated that all these findings implicate dopamine in motor disorders. Oleh Hornykiewicz, a young pharmacologist in Vienna, on

  14. Effective doping of low energy ions into superfluid helium droplets

    PubMed Central

    Zhang, Jie; Chen, Lei; Freund, William M.; Kong, Wei

    2015-01-01

    We report a facile method of doping cations from an electrospray ionization (ESI) source into superfluid helium droplets. By decelerating and stopping the ion pulse of reserpine and substance P from an ESI source in the path of the droplet beam, about 104 ion-doped droplets (one ion per droplet) can be recorded, corresponding to a pickup efficiency of nearly 1 out of 1000 ions. We attribute the success of this simple approach to the long residence time of the cations in the droplet beam. The resulting size of the doped droplets, on the order of 105/droplet, is measured using deflection and retardation methods. Our method does not require an ion trap in the doping region, which significantly simplifies the experimental setup and procedure for future spectroscopic and diffraction studies. PMID:26298127

  15. Thyroid Storm—A Review of Cases at University of California, San Francisco

    PubMed Central

    Roizen, Michael; Becker, Charles E.

    1971-01-01

    Retrospective study of the diagnosis and management of the 8 cases of thyroid storm in a series of 400 hyperthyroid patients led to conclusion that thyroid storm is a clinical diagnosis based on a life-endangering illness in a hyperthyroid patient whose hyperthyroidism has been severely exacerbated by a serious precipitating illness, and that storm is manifest by the symptoms of hyperpyrexia, tachycardia and striking alterations in consciousness. No laboratory tests were diagnostic of storm, and the underlying precipitating cause of thyroid storm was the major determinant of survival. Vigorous therapy must include blocking synthesis of thyroid hormones with antithyroid drugs, blocking release of preformed hormone with iodine, meticulous attention to hydration and supportive therapy, as well as correction of precipitating cause of storm. The blocking of the sympathetic nervous system with reserpine or guanethidine or with alpha and beta blocking drugs may be exceedingly hazardous and requires skillful management and constant monitoring in a critically ill patient. PMID:5110595

  16. Spectrophotometric determination of dihydralazine in pharmaceuticals after derivatization with 2-hydroxy-1-naphthaldehyde.

    PubMed

    Pous Miralles, G; García-Domenech, R; Mañes Vinuesa, J; Marí Buigues, J

    1993-08-01

    A sensitive and selective colorimetric assay has been developed for the determination of dihydralazine. The method is based on the interaction of dihydralazine with an ethanolic solution of 2-hydroxy-1-naphthaldehyde to yield a water-insoluble yellow product, 1,4-bis[(2-hydroxy-1-naphthyl)methylene hydrazine]phthazine. This colour can be quantified spectrophotometrically at 420 nm. The calibration curve was linear between 0.4 and 8 micrograms ml-1 of dihydralazine. The molar absorptivity at 420 nm is 24000 l mol-1 cm-1. The method was successfully applied to the determination of dihydralazine in mixtures containing other drugs (reserpine, hydrochlorothiazide, oxprenolol, xanthinol, rutoside, chlorthalidone and bietaserpine). PMID:8257729

  17. Behavior analysis and the growth of behavioral pharmacology.

    PubMed

    Laties, Victor G

    2003-01-01

    Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search for new drugs. Psychologists, most of whom were skilled in the behavior-analytic approach, started to assume prominent positions as authors and editors for the Journal of Pharmacology and Experimental Therapeutics as its emphasis on behavior increased. This also proved true with the other publications founded to deal with the popularity of behavioral pharmacology. Especially important were contributions by B. F. Skinner, Peter B. Dews, and Joseph V. Brady. PMID:22478405

  18. Effective doping of low energy ions into superfluid helium droplets

    SciTech Connect

    Zhang, Jie; Chen, Lei; Freund, William M.; Kong, Wei

    2015-08-21

    We report a facile method of doping cations from an electrospray ionization (ESI) source into superfluid helium droplets. By decelerating and stopping the ion pulse of reserpine and substance P from an ESI source in the path of the droplet beam, about 10{sup 4} ion-doped droplets (one ion per droplet) can be recorded, corresponding to a pickup efficiency of nearly 1 out of 1000 ions. We attribute the success of this simple approach to the long residence time of the cations in the droplet beam. The resulting size of the doped droplets, on the order of 10{sup 5}/droplet, is measured using deflection and retardation methods. Our method does not require an ion trap in the doping region, which significantly simplifies the experimental setup and procedure for future spectroscopic and diffraction studies.

  19. Gastroprotective activity of ginger zingiber officinale rosc., in albino rats.

    PubMed

    al-Yahya, M A; Rafatullah, S; Mossa, J S; Ageel, A M; Parmar, N S; Tariq, M

    1989-01-01

    The cytoprotective and gastric anti-ulcer studies of ginger have been carried out in albino rats. Cytodestruction was produced by 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl. Whereas gastric ulcers were produced by ulcerogenic agents including indomethacin, aspirin and reserpine, beside hypothermic restraint stress and by pylorus ligated Shay rat technique. The results of this study demonstrate that the extract in the dose of 500 mg/kg orally exert highly significant cytoprotection against 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl induced gastric lesions. The extract also prevented the occurrence of gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) and hypothermic restraint stress. These observations suggest cytoprotective and anti-ulcerogenic effect of the ginger. PMID:2589236

  20. Investigation of thin ZnO layers in view of laser desorption-ionization

    NASA Astrophysics Data System (ADS)

    Grechnikov, A. A.; Georgieva, V. B.; Alimpiev, S. S.; Borodkov, A. S.; Nikiforov, S. M.; Simanovsky, Ya O.; Dimova-Malinovska, D.; Angelov, O. I.

    2010-04-01

    Thin zinc oxide films (ZnO) were developed as a matrix-free platform for surface assisted laser desorption-ionization (SALDI) time-of-flight mass spectrometry. The ZnO films were deposited by RF magnetron sputtering of ZnO ceramic targets in Ar atmospheres on monocrystalline silicon. The generation under UV (355 nm) laser irradiation of positive ions of atenolol, reserpine and gramicidin S from the ZnO layers deposited was studied. All analytes tested were detected as protonated molecules with no or very structure-specific fragmentation. The mass spectra obtained showed low levels of chemical background noise. All ZnO films studied exhibited high stability and good reproducibility. The detection limits for test analytes are in the 10 femtomol range.

  1. Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.

    PubMed

    Holler, Jes Gitz; Slotved, Hans-Christian; Mølgaard, Per; Olsen, Carl Erik; Christensen, Søren Brøgger

    2012-07-15

    A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequently proved to be inhibitors of the NorA efflux pump in everted membrane vesicles. Compounds 5, 7, and 9 synergistically increased the effect of ciprofloxacin on Staphylococcus aureus. Our results suggest that chalcones might be developed into drugs for overcoming multidrug resistance based on efflux transporters of microorganisms. PMID:22682300

  2. Synthesis and Pharmacology of (Pyridin-2-yl)methanol Derivatives as Novel and Selective Transient Receptor Potential Vanilloid 3 Antagonists.

    PubMed

    Gomtsyan, Arthur; Schmidt, Robert G; Bayburt, Erol K; Gfesser, Gregory A; Voight, Eric A; Daanen, Jerome F; Schmidt, Diana L; Cowart, Marlon D; Liu, Huaqing; Altenbach, Robert J; Kort, Michael E; Clapham, Bruce; Cox, Phil B; Shrestha, Anurupa; Henry, Rodger; Whittern, David N; Reilly, Regina M; Puttfarcken, Pamela S; Brederson, Jill-Desiree; Song, Ping; Li, Bin; Huang, Susan M; McDonald, Heath A; Neelands, Torben R; McGaraughty, Steve P; Gauvin, Donna M; Joshi, Shailen K; Banfor, Patricia N; Segreti, Jason A; Shebley, Mohamad; Faltynek, Connie R; Dart, Michael J; Kym, Philip R

    2016-05-26

    Transient receptor potential vanilloid 3 (TRPV3) is a Ca(2+)- and Na(+)-permeable channel with a unique expression pattern. TRPV3 is found in both neuronal and non-neuronal tissues, including dorsal root ganglia, spinal cord, and keratinocytes. Recent studies suggest that TRPV3 may play a role in inflammation, pain sensation, and skin disorders. TRPV3 studies have been challenging, in part due to a lack of research tools such as selective antagonists. Herein, we provide the first detailed report on the development of potent and selective TRPV3 antagonists featuring a pyridinyl methanol moiety. Systematic optimization of pharmacological, physicochemical, and ADME properties of original lead 5a resulted in identification of a novel and selective TRPV3 antagonist 74a, which demonstrated a favorable preclinical profile in two different models of neuropathic pain as well as in a reserpine model of central pain. PMID:27077528

  3. Effect of central neurotropic substances on the hypophysisadrenal cortex system during immobilization of animals

    NASA Technical Reports Server (NTRS)

    Ryzhenkov, V. Y.

    1980-01-01

    The immobilization of guinea pigs for 5, 12, 24 and 48 hours, by securing to a slab, results in a persistent rise of the blood plasma 17-oxycorticosteroid concentration. Repeated administration of phenobarbital (50 mg/kg) and of the sodium salt of gamma-oxybutyric acid (500 mg/kg), as well as the combined administration of central m- and n-cholinolytics with small doses of phenobarbital tends to inhibit activation of the adrenal cortex during 48 hour immobilization of the animals. Repeated administration of aminazine (20 mg/kg) tends to decrease activation of the adrenal cortex. The administration of reserpine (0.1-5 mg/kg) 12-18 hours before immobilization of guinea pigs increases the response of the hypophysis-adrenal cortex system.

  4. Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment

    PubMed Central

    AbdelHafez, ElShimaa M. N.; Diamanduros, Andrew; Negureanu, Lacramioara; Luy, Yan; Bean, J. Hayley; Zielke, Katherine; Crowe, Brittany; Vasilyeva, Aksana; Clodfelter, Jill E.; Aly, Omar M.; Abuo-Rahma, Gamal El-Din A. A.; Scarpinato, Karin D.; Salsbury, Freddie R.; King, S. Bruce

    2014-01-01

    We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing. PMID:25485184

  5. Natural substances in psychiatry (Ginkgo biloba in dementia).

    PubMed

    Itil, T; Martorano, D

    1995-01-01

    Natural substances and/or their synthetically developed active ingredients are frequently used in medicine. In psychiatry, two of the most well known natural compounds are reserpine and Ginkgo biloba extract (EGb). EGb is among the most popular over-the-counter medicines in Europe and is also available in the United States, primarily in health food stores. Already the European medical community has recognized EGb as an effective compound in the treatment of cerebral insufficiency. In a pilot bioequivalency study, the effects of three different commercially available EGb products were examined. Findings indicated significant quantitative central nervous system (CNS) effects in, at least, one of the three. Furthermore, the CNS effects of Ginkgold were similar to other psychoactive compounds classified as cognitive activators. Recent studies in which EGb 761 demonstrated therapeutic effects in the treatment of dementia have earned EGb the approval of the German BGA (Bundesgesundheit Amt) for use in the treatment of dementia. PMID:7675979

  6. RU24722 induces spatially organized phenotypic plasticity in the locus coeruleus.

    PubMed

    Debure, L I; Bezin, L; Ginovart, N; Rousset, C; Pujol, J F; Weissmann, D

    1994-09-01

    The plasticity of tyrosine hydroxylase (TH) expression in rat locus coeruleus (LC) was evaluated after RU24722 TH induction using, as a new parameter of characterization, the quantitative topology of LC defined by TH-positive cells. This new phenotype was spatially organized into cell subpopulations in the medial LC, dorsal and ventro-lateral to the initial perikaryal space. Reserpine and parachlorophenylalanine, which elicited a similar increase in the TH content, failed to induce a significant change in the number of TH-expressing cells. Activation of TH expression is not sufficient to reveal the existence of such a plasticity and some original but still unknown mechanism(s) of control of TH expression is affected by RU24722. PMID:7827334

  7. Reproducible preparation of nanospray tips for capillary electrophoresis coupled to mass spectrometry using 3D printed grinding device.

    PubMed

    Tycova, Anna; Prikryl, Jan; Foret, Frantisek

    2016-04-01

    The use of high quality fused silica capillary nanospray tips is critical for obtaining reliable and reproducible electrospray/MS data; however, reproducible laboratory preparation of such tips is a challenging task. In this work, we report on the design and construction of low-cost grinding device assembled from 3D printed and commercially easily available components. Detailed description and characterization of the grinding device is complemented by freely accessible files in stl and skp format allowing easy laboratory replication of the device. The process of sharpening is aimed at achieving maximal symmetricity, surface smoothness and repeatability of the conus shape. Moreover, the presented grinding device brings possibility to fabricate the nanospray tips of desired dimensions regardless of the commercial availability. On several samples of biological nature (reserpine, rabbit plasma, and the mixture of three aminoacids), performance of fabricated tips is shown on CE coupled to MS analysis. The special interest is paid to the effect of tip sharpness. PMID:26626777

  8. Behavior analysis and the growth of behavioral pharmacology

    PubMed Central

    Laties, Victor G.

    2003-01-01

    Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search for new drugs. Psychologists, most of whom were skilled in the behavior-analytic approach, started to assume prominent positions as authors and editors for the Journal of Pharmacology and Experimental Therapeutics as its emphasis on behavior increased. This also proved true with the other publications founded to deal with the popularity of behavioral pharmacology. Especially important were contributions by B. F. Skinner, Peter B. Dews, and Joseph V. Brady. PMID:22478405

  9. Effect of toloxatone on behaviour of primates.

    PubMed

    Giono-Barber, H; Giono-Barber, P; Milhaud, C L; Klein, M J; Gouret, C; Raynaud, G

    1977-01-01

    1. The effects of (3-methyl)-3-phenyl-5-hydroxy-methyl-2-oxazolidinone (toloxatone) were studied on the behaviour of three species of primates: baboon, rhesus monkeys and chimpanzee. 2. The activity against reserpine-induced depression is observed in baboon as in rodents. 2. The administration of toloxatone induces three effects which probably have the same origin: suppression of feeding inhibition of the subordinate baboon, improvement of escape reaction in the conditioned chimpanzee, increase in general activity and the active component of social behaviour in grouped rhesus monkeys. These three effects can be interpreted as resulting from the stimulating effect of toloxatone, or more precisely from a disinhibiting effect. 4. Contrary to amphetamine, toloxatone does not induce, even at high or repeated doses, behavioural disturbances. PMID:409416

  10. Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L.

    PubMed Central

    Tian, Jingwei; Zhang, Fangxi; Cheng, Jucan; Guo, Shuren; Liu, Pinglan; Wang, Hongbo

    2014-01-01

    Adhyperforin is a novel constituent of Hypericum perforatum L., but its antidepressant-like activity remains unclear. To explore that, several well-validated animal models of depression as well as neurotransmitter reuptake and transporter binding assays were conducted. The results showed adhyperforin could reduce the immobility time of mice in the forced swimming test and tail suspension assay, antagonize the behaviors induced by reserpine, and have no effect on locomotor activity. Furthermore, following establishment of a chronic unpredictable mild stress model, adhyperforin increased the number of crossings and rearings in rats in the open field test and increased the sucrose consumption. Finally, adhyperforin inhibited uptake of serotonin, norepinephrine, and dopamine, and displayed robust binding affinities for the serotonin and norepinephrine transporters. Overall, the current study provides the first evidence that adhyperforin is a novel, active ingredient of Hypericum perforatum L. with robust antidepressant-like activity. PMID:25005489

  11. Changes in sensitivity of the isolated guinea-pig vas deferens induced by a lyophilized Phoradendron latifolium leaf infusion.

    PubMed

    Queiroz-Neto, A; Melito, I

    1990-02-01

    The effect of a lyophilized mistletoe infusion (LMI) was studied on isolated guinea-pig vas deferens. LMI caused a contraction which was partially blocked by phentolamine but not by atropine. LMI caused a shift to the left of the norepinephrine concentration-effect curve (CEC), an effect which appeared to be blocked by atropine and was absent in animals previously treated with reserpine and alpha-methyl-para-tyrosine. The increase of the norepinephrine maximal response induced by LMI was not blocked by atropine or pharmacological denervation. LMI caused a shift to the right of the acetylcholine CEC and had no effect on the acetylcholine maximal response. These results suggest that the effects seem to be due mainly to the presence of potassium ion in the LMI; however, the participation of muscarinic agonist(s) of reduced intrinsic activity or some tyramine-like substance could not be ruled out. PMID:2329809

  12. In vivo (/sup 3/H)spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    SciTech Connect

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-06-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist (3H)spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo (3H)spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of (3H)spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound (3H)spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to (3H)spiperone injection resulted in a selective increase of in vivo (3H)spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.

  13. Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues

    SciTech Connect

    Eisenhofer, G.; Hovevey-Sion, D.; Kopin, I.J.; Miletich, R.; Kirk, K.L.; Finn, R.; Goldstein, D.S.

    1989-01-01

    The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine.

  14. Gastric anti-ulcer and cytoprotective effect of selenium in rats

    SciTech Connect

    Parmar, N.S.; Tariq, M.; Ageel, A.M.

    1988-01-01

    Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl was significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.

  15. [A unique psychopharmacologic profile of adrafinil in mice].

    PubMed

    Rambert, F A; Pessonnier, J; de Sereville, J E; Pointeau, A M; Duteil, J

    1986-01-01

    The following psychopharmacological effects of adrafinil have been observed in mice: increase in locomotor activity (64-256 mg.kg-1), antagonism (16-128 mg.kg-1) of the hypnotic effects of barbitone but not of pentobarbitone, reduction of immobility duration in the forced swimming test (16-256 mg.kg-1); slight antagonism (256 mg.kg-1) of electroshock-induced convulsions; no modification of rectal temperature; no stereotyped or climbing behaviour; no increase in lethality in aggregated mice (LD50 isolated = 1022 mg.kg-1, LD50 aggregated = 859 mg.kg-1); lack of effects on the provisional tests for antidepressants: no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia but potentiation of yohimbine-induced toxicity; lack of peripheral sympathetic effects (no mydriasis, no salivation, no contraction of the pilomotor muscles, no antagonism of reserpine-induced ptosis); lack of peripheral anticholinergic effects (no mydriasis, no antagonism of oxotremorine-induced salivation or lacrimation). As compared to no analeptic, anticholinergic or antidepressant drugs, adrafinil shows a unique behavioural profile in mice defined on the one hand by a specific stimulant activity associated with antidepressant-like effects that do no seem related to a beta-adrenergic mechanism and on the other hand by a lack of dopaminergic effects. Most adrafinil-induced effects (increase in locomotor activity, reduction of immobility duration in the forced swimming test) may correspond to a central alpha 1-adrenergic stimulation, but the unexpected lack of peripheral sympathetic effects remains unexplained. PMID:3713198

  16. Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage

    PubMed Central

    Blackmore, Colin G; Varro, Andrea; Dimaline, Rod; Bishop, Lisa; Gallacher, David V; Dockray, Graham J

    2001-01-01

    The acidic interior of neuroendocrine secretory vesicles provides both an energy gradient for amine-proton exchangers (VMATs) to concentrate small transmitter molecules, for example catecholamines, and an optimal pH for the prohormone convertases which cleave hormone precursors. There is evidence that VMAT activity modulates prohormone cleavage, but in the absence of measurements of pH in secretory vesicles in intact cells, it has not been possible to establish whether these effects are attributable to raised intravesicular pH due to proton transport through VMATs. Clones were generated of the hamster insulinoma cell line HIT-T15 expressing a pH-sensitive form of green fluorescent protein (GFP-F64L/S65T) targeted to secretory vesicles, with and without co-expression of VMAT2. In order to study prohormone cleavage, further clones were generated that expressed preprogastrin with and without co-expression of VMAT2. Confocal microscopy of GFP fluorescence indicated that the pH in the secretory vesicles was 5.6 in control cells, compared with 6.6 in cells expressing VMAT2; the latter was reduced to 5.8 by the VMAT inhibitor reserpine. Using a pulse-chase labelling protocol, cleavage of 34-residue gastrin (G34) was found to be inhibited by co-expression with VMAT2, and this was reversed by reserpine. Similar effects on vesicle pH and G34 cleavage were produced by ammonium chloride. We conclude that VMAT expression confers the linked abilities to store biogenic amines and modulate secretory vesicle pH over a range influencing prohormone cleavage and therefore determining the identity of regulatory peptide secretory products. PMID:11251044

  17. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014).

    PubMed

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995-2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  18. Pharmacological properties of beta-amyrin palmitate, a novel centrally acting compound, isolated from Lobelia inflata leaves.

    PubMed

    Subarnas, A; Tadano, T; Oshima, Y; Kisara, K; Ohizumi, Y

    1993-06-01

    Effects of beta-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, beta-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg-1). beta-Amyrin palmitate (5, 10 and 20 mg kg-1) or mianserin (5, 10 and 20 mg kg-1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg-1) increased locomotor activity and potentiated methamphetamine-induced hyperactivity. beta-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg-1) and imipramine (10 and 20 mg kg-1) antagonized the reserpine-induced effect. Unlike imipramine, beta-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. beta-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg-1) decreased it in a dose-dependent manner. A potentiating effect of beta-amyrin palmitate (5, 10 and 20 mg kg-1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg-1) but weaker than that of mianserin (2.5, 5 and 10 mg kg-1). These results suggest that beta-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8103103

  19. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)

    PubMed Central

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M.; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  20. Effect of venlafaxine on experimental colitis in normal and reserpinised depressed rats

    PubMed Central

    Minaiyan, Mohsen; Hajhashemi, Valiollah; Rabbani, Mohammad; Fattahian, Ehsan; Mahzouni, Parvin

    2015-01-01

    Psychological disorders such as depression have more prevalence in inflammatory bowel disease patients and can exacerbate the clinical course of the disease, so anti-depressant therapy may have a potential to positively impact the disease course. On the other hand several antidepressant drugs have shown anti-inflammatory and immunomodulatory properties. Thus, this study aimed to explore the beneficial effects of venlafaxine on experimental colitis in normal and reserpinised depressed rats. Acetic acid colitis was induced in both reserpinised and non-reserpinised rats. Reserpinised groups received reserpine at dose of 6 mg/kg i.p.1 h prior to colitis induction and then treated with venlafaxine at doses of 10, 20, 40 mg/kg given i.p. 2 h after induction of colitis and daily for 4 consecutive days. Non-reserpinised groups treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic, histological and myeloperoxidase activity measurements. Results showed that reserpine at dose of 6 mg/kg exacerbated the colitis damage. Compared to acetic acid control, venlafaxine at dose of 40 mg/kg as well as dexamethasone significantly improved colitis parameters in both reserpinised and non-reserpinised animals. Venlafaxine reduced inflammatory injury in this animal model of induced ulcerative colitis. These effects are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug. PMID:26600857

  1. Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems.

    PubMed

    Matsumoto, K; Mizowaki, M; Suchitra, T; Murakami, Y; Takayama, H; Sakai, S; Aimi, N; Watanabe, H

    1996-12-12

    Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that is known to exhibit narcotic-like activity. In this study, we investigated the roles of central monoaminergic systems in the antinociceptive action of mitragynine by means of the tail-pinch and hot-plate tests in mice. Mitragynine (1.0-10 micrograms) injected i.c.v. exerted a dose-dependent antinociceptive activity in both tests. The activity of mitragynine (10 micrograms, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalnine treatment, whereas the antinociceptive activity of morphine (3 micrograms) given i.c.v. in this test was attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by the alpha 2-adrenoceptor antagonist, idazoxan (10 micrograms), and cyproheptadine (1 microgram) administered intrathecally (i.t.). On the other hand, the antinociceptive action of i.c.v. mitragynine (10 micrograms) in the hot-plate test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not by p-chlorophenylalanine treatment. This action was also antagonized by i.t. injection of idazoxan (10 micrograms). These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of supraspinally administered mitragynine on the mechanical noxious stimulation, while the descending noradrenergic system predominantly contributes to the effect of supraspinal mitragynine on the thermal noxious stimulation. The mechanisms underlying the suppressive action of mitragynine on the nociceptive response may differ from those of morphine in mice. PMID:8982722

  2. High affinity binding of [3H]-tyramine in the central nervous system.

    PubMed Central

    Vaccari, A.

    1986-01-01

    Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximately 30 times higher than that in the cerebellum, with similar dissociation constants (KD). The binding process of [3H]-pTA involved the dopamine system, inasmuch as (a) highest binding capacity was associated with dopamine-rich regions; (b) dopamine and pTA equally displaced specifically bound [3H]-pTA; (c) there was a severe loss in striatal binding capacity for [3H]-pTA and, reportedly, for [3H]-dopamine, following unilateral nigrostriatal lesion; (d) acute in vivo reserpine treatment markedly decreased the density of [3H]-pTA and, reportedly, of [3H]-dopamine binding sites. In competition experiments [3H]-pTA binding sites, though displaying nanomolar affinity for dopamine, revealed micromolar affinities for the dopamine agonists apomorphine and pergolide, and for several dopamine antagonists, while having very high affinity for reserpine, a marker for the catecholamine transporter in synaptic vesicles. The binding process of [3H]-pTA was both energy-dependent (ouabain-sensitive), and ATP-Mg2+-insensitive; furthermore, the potencies of various drugs in competing for [3H]-pTA binding to rat striatal membranes correlated well (r = 0.96) with their reported potencies in inhibiting [3H]-dopamine uptake into striatal synaptosomes. It is concluded that [3H]-pTA binds at a site located on/within synaptic vesicles where it is involved in the transport mechanism of dopamine. PMID:3801770

  3. The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity

    PubMed Central

    Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhn, Donald M.

    2009-01-01

    The neurotransmitter dopamine (DA) has long been implicated as a participant in the neurotoxicity caused by methamphetamine (METH), yet, its mechanism of action in this regard is not fully understood. Treatment of mice with the tyrosine hydroxylase (TH) inhibitor α-methyl-p-tyrosine (AMPT) lowers striatal cytoplasmic DA content by 55% and completely protects against METH-induced damage to DA nerve terminals. Reserpine, by disrupting vesicle amine storage, depletes striatal DA by more than 95% and accentuates METH-induced neurotoxicity. L-DOPA reverses the protective effect of AMPT against METH and enhances neurotoxicity in animals with intact TH. Inhibition of MAO-A by clorgyline increases pre-synaptic DA content and enhances METH striatal neurotoxicity. In all conditions of altered pre-synaptic DA homeostasis, increases or decreases in METH neurotoxicity paralleled changes in striatal microglial activation. Mice treated with AMPT, L-DOPA, or clorgyline + METH developed hyperthermia to the same extent as animals treated with METH alone, whereas mice treated with reserpine + METH were hypothermic, suggesting that the effects of alterations in cytoplasmic DA on METH neurotoxicity were not strictly mediated by changes in core body temperature. Taken together, the present data reinforce the notion that METH-induced release of DA from the newly synthesized pool of transmitter into the extracellular space plays an essential role in drug-induced striatal neurotoxicity and microglial activation. Subtle alterations in intracellular DA content can lead to significant enhancement of METH neurotoxicity. Our results also suggest that reactants derived from METH-induced oxidation of released DA may serve as neuronal signals that lead to microglial activation early in the neurotoxic process associated with METH. PMID:18088364

  4. Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart

    SciTech Connect

    Nguyen, N.T.B.; DeGrado, T.R.; Chakraborty, P.

    1997-05-01

    The kinetics of EPI were studied in the isolated rat heart model to evaluate {sup 11}C-epinephrine (EPI) as a radiotracer for the assessment of sympathetic neuronal function in the heart. Isolated rat hearts were perfused in a working mode. Carbon-11-EPI was added to the perfusate during wash-in period of 20 min, followed by a washout period of 40 min. Radioactivity in the heart was externally monitored and time-activity curves were recorded as a function of time. Effluent samples were collected throughout each study to determine the fraction of {sup 11}C radioactivity as intact tracer. Time-activity curves of control hearts showed that {sup 11}C-EPI is taken up and retained by the myocardium. Desipramine inhibition (DMI) of uptake-1 resulted in a significant decrease in myocardial uptake and retention of {sup 11}C-EPI by 91% compared to controls. Addition of DMI to the perfusion medium during washout did not affect kinetics of {sup 11}C-EPI compared to control hearts. Reserpine pretreated rat hearts also showed significant decrease in tracer retention of 95% compared to controls. The metabolic data showed that, in control conditions, about 61% of {sup 11}C-EPI taken up by the rat heart is rapidly metabolized and released. Carbon-11-EPI traces sympathetic nerve terminals in the isolated rat heart. Uptake blockade by DMI and reserpine suggest that uptake and storage of {sup 11}C-EPI appear to be similar to that of norepinephrine. However, the prominent metabolic pathway warrants further consideration. These results suggest that {sup 11}C-EPI may be a suitable radiolabeled tracer for the evaluation of sympathetic vesicular function of the heart by PET. 23 refs., 3 figs., 3 tabs.

  5. Design, Development and Rationalization of Sarpagandha Ghanvati.

    PubMed

    Pundarikakshudu, K; Bhatt, C J

    2015-01-01

    Sarpagandha ghanvati is a classical Ayurvedic formulation widely prescribed for anxiety and insomnia. It contains Sarpagandha (roots of Rauwolfia serpentina L. (Benth.) Ex Kurz; Family: Apocyanaceae), Khurasani ajowan (Hyocyamus niger L.; Family: Solanaceae) seeds, Jatamansi (Nardostachys jatamansi DC. Family: Valerianaceae) roots and Pipplamul (root of Piper longum L.; Family: Piperaceae). The objective of this study was to make a comparative evaluation of Ghanvatis and tablets of this formulation. Two tablet formulations were prepared; one incorporating only powders of all ingredients; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Similarly, two types of Sarpagandha ghanvati pills were prepared; one as per Ayurvedic Formulary of India; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Alcohol extracted 0.22% w/w of total alkaloids as against 0.061% w/w extracted by water. Tablets prepared with powders of all the ingredients had friability more than 3.0% where as those prepared with ethanol extract had very low friability. Ghanvatis, prepared as per the Ayurvedic formulary, did not show reserpine although other alkaloids were present. They showed less content uniformity and lower drug release. Ethanol extracted reserpine along with other alkaloids. Ghanvatis made with the alcoholic extracts exhibited better content uniformity and drug release than the traditional formulation. Tablets prepared with powders or extracts of the ingredients exhibited good content uniformity but the release of alkaloids from the tablets of powders was only 80%. Tablets of the extracts had good content uniformity with 90% release of the total alkaloids. Tablets prepared with alcoholic extracts using 1% polyvinylpyrrolidone as binder and 5% dried starch powder as disintegrating agent confirmed to all the requirements. Thus, the study shows tablets made with the extracts are superior to

  6. Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection.

    PubMed

    Wagner, Michel; Varesio, Emmanuel; Hopfgartner, Gérard

    2008-09-01

    We present herein an ultra-fast quantitative assay for the quantitation of saquinavir in human plasma, without prior chromatographic separation, with matrix-assisted laser desorption/ionization using the selected reaction monitoring quantitation mode (MALDI-SRM/MS). The method was found to be linear from 5 to 10,000 ng/ml using pentadeuterated saquinavir (SQV-d5) as an internal standard, and from 5 to 1000 ng/ml using reserpine as internal standard (IS). Accuracy and precision were in the range of 101-108%, 3.9-11% with SQV-d5 and in the range 93-108%, 3.5-15% with reserpine. Plasma samples (250 microl) were extracted with a mixture of ethyl acetate/hexane. MALDI spotting of the extract was automated using electrodeposition and the dried droplet method using alpha-cyano-4-hydroxycinnamic acid (CHCA) as matrix. A 96 spots MALDI plate was prepared within 20 min in a fully unattended manner. Each sample was spotted four times and quantitation was based on the average of their analyte/IS area ratio. Samples were analyzed on a triple quadrupole linear ion trap (QqQ(LIT)) equipped with a high repetition laser source (1000 Hz). The analysis time of one sample was approximately 6 s, therefore 96 samples could be analyzed in less than 10 min. With liquid-liquid extraction sample preparation no significant matrix effects were observed. Moreover, the assay showed sufficient selectivity for samples to be analyzed at the lower limit of quantification (LLOQ) in the presence of other antiretroviral drugs, without prior chromatographic steps. In parallel, to assess the selectivity of the assay with real samples, a liquid chromatography (LC)-SRM/MS method was developed and a cross validation with clinical samples was successfully performed. PMID:18657486

  7. Distribution and expression of the Ade multidrug efflux systems in Acinetobacter baumannii clinical isolates.

    PubMed

    Pagdepanichkit, Sirawit; Tribuddharat, Chanwit; Chuanchuen, Rungtip

    2016-09-01

    One hundred Acinetobacter baumannii clinical isolates were examined for inhibitory effect of reserpine and carbonyl cyanide m-chlorophenylhydrazone (CCCP) on the antimicrobial susceptibility and expression of 4 resistant-nodulation-cell division (RND)-type multidrug efflux systems, including AdeABC, AdeDE, AdeIJK, and AdeFGH, using RT-PCR. Ten A. baumannii isolates expressing AdeABC, AdeIJK, or AdeFGH were randomly selected for determination of transcription level and regulatory mutations. While all the isolates were resistant to multiple drugs, the reserpine and CCCP experiment showed that the multidrug resistance phenotype in most A. baumannii isolates was associated with efflux pumps. Most isolates expressed at least one of the RND-type efflux pumps tested (97%). AdeIJK expression was most common (97%), but none of the isolates produced AdeDE. Fifty-two percent of the A. baumannii isolates simultaneously produced up to 3 RND-type efflux systems (i.e., AdeABC, AdeFGH, and AdeIJK). No good correlation between the expression of RND-type efflux pumps and the type of antimicrobial resistance was observed. Overexpression of AdeABC, AdeIJK, and AdeFGH was not always related to the presence of mutations in their corresponding regulatory genes. This study highlights (i) the universal presence of the RND-type efflux pumps with variable levels of expression level among the A. baumannii in this collection and (ii) the complexity of their regulation of expression. PMID:27332787

  8. Design, Development and Rationalization of Sarpagandha Ghanvati

    PubMed Central

    Pundarikakshudu, K.; Bhatt, C. J.

    2015-01-01

    Sarpagandha ghanvati is a classical Ayurvedic formulation widely prescribed for anxiety and insomnia. It contains Sarpagandha (roots of Rauwolfia serpentina L. (Benth.) Ex Kurz; Family: Apocyanaceae), Khurasani ajowan (Hyocyamus niger L.; Family: Solanaceae) seeds, Jatamansi (Nardostachys jatamansi DC. Family: Valerianaceae) roots and Pipplamul (root of Piper longum L.; Family: Piperaceae). The objective of this study was to make a comparative evaluation of Ghanvatis and tablets of this formulation. Two tablet formulations were prepared; one incorporating only powders of all ingredients; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Similarly, two types of Sarpagandha ghanvati pills were prepared; one as per Ayurvedic Formulary of India; the other with ethanol extracts of the first three ingredients and powder of Piper longum root. Alcohol extracted 0.22% w/w of total alkaloids as against 0.061% w/w extracted by water. Tablets prepared with powders of all the ingredients had friability more than 3.0% where as those prepared with ethanol extract had very low friability. Ghanvatis, prepared as per the Ayurvedic formulary, did not show reserpine although other alkaloids were present. They showed less content uniformity and lower drug release. Ethanol extracted reserpine along with other alkaloids. Ghanvatis made with the alcoholic extracts exhibited better content uniformity and drug release than the traditional formulation. Tablets prepared with powders or extracts of the ingredients exhibited good content uniformity but the release of alkaloids from the tablets of powders was only 80%. Tablets of the extracts had good content uniformity with 90% release of the total alkaloids. Tablets prepared with alcoholic extracts using 1% polyvinylpyrrolidone as binder and 5% dried starch powder as disintegrating agent confirmed to all the requirements. Thus, the study shows tablets made with the extracts are superior to

  9. GABAA receptor-mediated positive inotropism in guinea-pig isolated left atria: evidence for the involvement of capsaicin-sensitive nerves.

    PubMed Central

    Maggi, C. A.; Giuliani, S.; Manzini, S.; Meli, A.

    1989-01-01

    1. Isolated left atria from reserpine-pretreated guinea-pigs, electrically driven (3 Hz) in the presence of atropine (1 microM), phentolamine (0.3 microM) and propranolol (1 microM), responded to a train of stimuli (10 Hz for 2.5s) with a delayed neurogenic positive inotropic response which was insensitive to hexamethonium (10 microM) but abolished by either tetrodotoxin (1 microM), omega-conotoxin (0.1 microM), in vitro capsaicin desensitization or desensitization to calcitonin gene-related peptide (CGRP). 2. In these experimental conditions, gamma-aminobutyric acid (GABA) produced a concentration-related (10 microM-1 mM) positive inotropic response similar to that produced by electrical field stimulation. The effect of GABA was competitively antagonized by bicuculline methiodide (10 microM), a GABAA receptor antagonist. 3. The selective GABAA receptor agonists, muscimol and homotaurine mimicked the positive inotropic effect of GABA while baclofen, the selective GABAB receptor agonist, did not. 4. The action of GABA (1 mM) was abolished by either tetrodotoxin (1 microM), omega-conotoxin (0.1 microM), in vitro capsaicin desensitization or desensitization to CGRP, while it was unaffected by hexamethonium. In contrast, the inotropic response to CGRP was unaffected by tetrodotoxin, omega-conotoxin, bicuculline methiodide, hexamethonium or in vitro capsaicin desensitization, but was abolished by CGRP desensitization. 5. In the spontaneously beating guinea-pig right atrium, GABA (1 microM) produced a small and transient positive chronotropic effect that was no longer observed after in vitro desensitization with capsaicin (1 microM). 6. In the guinea-pig isolated perfused heart from reserpine-pretreated animals (with atropine, phentolamine and propranolol in the perfusion medium), GABA (1 microM) produced a transient tachycardia and a small increase in coronary flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2541852

  10. Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair.

    PubMed

    Yu, Hai-Ling; Sun, Lian-Ping; Li, Miao-Miao; Quan, Zhe-Shan

    2015-04-23

    Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In the present study, we investigated the antidepressant- like potential of OEA in mice in comparison with clomipramine (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20 mL/kg, p.o.), OEA (2.5, 5-10mg/kg, p.o.), or Cp (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels. Likewise, in the drug-induced model of depression, OEA was given once daily at 10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4 mg/kg, i.p.) and the rectal temperature was measured at different time points. Consequently, head twitch behavior induced by intraperitoneal injection of 5-hydroxy-tryptophan (5-HTP; 300 mg/kg) were determined. The experimental data showed that OEA (2.5-10mg/kg) treatment significantly decreased the immobility as compared to the control group, and OEA (10mg/kg) treatment significantly increased 5-HTP-induced head twitch behavior and reversed reserpine-induced hypothermia and increased cerebral levels of NE and 5-HT. Thus, the antidepressant effects of OEA may be related to regulating central monoamine neurotransmitters. PMID:25778418

  11. Resistance of Stenotrophomonas maltophilia to Fluoroquinolones: Prevalence in a University Hospital and Possible Mechanisms

    PubMed Central

    Jia, Wei; Wang, Jiayuan; Xu, Haotong; Li, Gang

    2015-01-01

    Objective: The purpose of this study was to investigate the clinical distribution and genotyping of Stenotrophomonas maltophilia, its resistance to antimicrobial agents, and the possible mechanisms of this drug resistance. Methods: S. maltophilia isolates were collected from clinical specimens in a university hospital in Northwestern China during the period between 2010 and 2012, and were identified to the species level with a fully automated microbiological system. Antimicrobial susceptibility testing was performed for S. maltophilia with the Kirby-Bauer disc diffusion method. The minimal inhibitory concentrations (MICs) of norfloxacin, ofloxacin, chloramphenicol, minocycline, ceftazidime, levofloxacin and ciprofloxacin against S. maltophilia were assessed using the agar dilution method, and changes in the MIC of norfloxacin, ciprofloxacin and ofloxacin were observed after the addition of reserpine, an efflux pump inhibitor. Fluoroquinolone resistance genes were detected in S. maltophilia using a polymerase chain reaction (PCR) assay, and the expression of efflux pump smeD and smeF genes was determined using a quantitative fluorescent (QF)-PCR assay. Pulsed-field gel electrophoresis (PFGE) was employed to genotype identified S. maltophilia isolates. Results: A total of 426 S. maltophilia strains were isolated from the university hospital from 2010 to 2012, consisting of 10.1% of total non-fermentative bacteria. The prevalence of norfloxacin, ciprofloxacin and ofloxacin resistance was 32.4%, 21.9% and 13.2% in the 114 S. maltophilia isolates collected from 2012, respectively. Following reserpine treatment, 19 S. maltophilia isolates positive for efflux pump were identified, and high expression of smeD and smeF genes was detected in two resistant isolates. gyrA, parC, smeD, smeE and smeF genes were detected in all 114 S. maltophilia isolates, while smqnr gene was found in 25.4% of total isolates. Glu-Lys mutation (GAA-AAA) was detected at the 151th amino acid of the

  12. Rapid Drug Tolerance and Dramatic Sterilizing Effect of Moxifloxacin Monotherapy in a Novel Hollow-Fiber Model of Intracellular Mycobacterium kansasii Disease

    PubMed Central

    Srivastava, Shashikant; Pasipanodya, Jotam; Sherman, Carleton M.; Meek, Claudia; Leff, Richard

    2015-01-01

    Mycobacterium kansasii is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed. Moxifloxacin has good MICs for M. kansasii. However, good preclinical models to identify optimal doses currently are lacking. We developed a novel hollow fiber system model of intracellular M. kansasii infection. We indexed the efficacy of the standard combination regimen, which was a kill rate of −0.08 ± 0.05 log10 CFU/ml/day (r2 = 0.99). We next performed moxifloxacin dose-effect and dose-scheduling studies at a half-life of 11.1 ± 6.47 h. Some systems also were treated with the efflux pump inhibitor reserpine. The highest moxifloxacin exposure, as well as lower exposures plus reserpine, sterilized the cultures by day 7. This suggests that efflux pump-mediated tolerance at low ratios of the area under the concentration-time curve from 0 to 24 h (AUC0–24) to MICs is an early bacterial defense mechanism but is overcome by higher exposures. The highest rate of moxifloxacin monotherapy sterilization was −0.82 ± 0.15 log10 CFU/ml/day (r2 = 0.97). The moxifloxacin exposure associated with 80% of maximal kill (EC80) was an AUC0–24/MIC of 317 (the non-protein-bound moxifloxacin AUC0–24/MIC was 158.5). We performed Monte Carlo simulations of 10,000 patients in order to identify the moxifloxacin dose that would achieve or exceed the EC80. The simulations revealed an optimal moxifloxacin dose of 800 mg a day. The MIC susceptibility breakpoint at this dose was 0.25 mg/liter. Thus, moxifloxacin, at high enough doses, is suitable to study in patients for the potential to add rapid sterilization to the standard regimen. PMID:25645830

  13. Benzalkonium chloride and heavy-metal tolerance in Listeria monocytogenes from retail foods.

    PubMed

    Xu, Dongyang; Li, Yanli; Zahid, M Shamim Hasan; Yamasaki, Shinji; Shi, Lei; Li, Jian-rong; Yan, He

    2014-11-01

    Phenotypic and genotypic tolerance in 71 Listeria monocytogenes isolates from different varieties of foods to benzalkonium chloride (BC) and cadmium were investigated by susceptibility test and molecular methods. To investigate the role of efflux pumps in BC tolerance, reserpine, an efflux pump inhibitor, was added to the BC tolerant strains. Tolerance to BC and cadmium were 26.8% (19/71) and 49.3% (35/71) respectively. Strains with BC tolerance were significantly more frequent among those of serotype 4b (100%, 6/6) than among those of serotype 1/2a (or 3a) (13.5%, 5/37), which represent the predominant number of strains (52.1%, 37/71). Tolerance to cadmium was encountered among 62.2% (23/37) and 50.0% (3/6) of the serotype 1/2a (or 3a) and 4b strains, respectively, and among 19.0% (4/21) of the strains of the serotype 1/2c. All of the 10 (14.1%) isolates found to be BC and cadmium co-tolerance were isolated from raw meat or quick-frozen food made of wheat flour and rice. Five multi-drug resistant strains were tolerant to cadmium as well. Among 71 isolates examined, one contained qacA and three contained qacEΔ1-sul. To the best of our knowledge, this is the first detection of qacA and qacEΔ1-sul in L. monocytogenes, an indication of the possible horizontal transfer of the two genes. Addition of reserpine to the tolerant strains resulted in the loss of tolerance among seven out of 19 BC strains, suggesting a certain role the efflux pump played in mediating BC tolerance. Of the three distinct cadA types known to date in L. monocytogenes, the cadA1 and cadA2 genes were detected among 24 (33.8%) and three (4.2%) isolates respectively. The presence of cadA1 and cadA2 largely corresponded to the susceptibility phenotype. A subset (9/35 [25.7%]) of the cadmium-tolerant isolates lacked the known cadmium resistance determinants. These findings suggest that food products could act as a reservoir for L. monocytogenes harboring tolerance to BC and cadmium and will further

  14. Sympathomimetic effects of Scoparia dulcis L. and catecholamines isolated from plant extracts.

    PubMed

    Freire, S M; Torres, L M; Souccar, C; Lapa, A J

    1996-06-01

    The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro. Administration of the extract (0.5-2 mg kg-1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the alpha-adrenoceptor antagonist prazosin (1 mg kg-1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1-3 x 10(3) micrograms mL-1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10(-8)-10(-4)M). Prazosin (10(-7)M) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 micrograms mL-1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 microgram mL-1). In preparations of guinea-pig tracheal rings the aqueous fraction (1-3 x 10(3) micrograms mL-1) relaxed the muscle contraction induced by histamine (10(-4) M) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 microM). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract. The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is

  15. [Treatment of severe hypertension in pregnancy].

    PubMed

    Oney, T; Weitzel, H

    1991-01-01

    Treatment of severe hypertension in pregnancy, particularly in preeclampsia and eclampsia, is a great challenge to the obstetrician and requires prompt and expert management. Application of antihypertensive agents is limited during pregnancy because of possible side effects, particularly impairment of the fetal state. The following survey present a detailed discussion on the substances suitable for treating hypertensive emergencies in pregnancy and their side effects. Despite restricted therapeutic possibilities, safe and successful treatment of severe hypertension during pregnancy can best be performed with dihydralazine and diazoxide, which achieve their effect by reducing the peripheral vascular resistance. If the blood pressure cannot be adequately reduced with these substances, treatment can be continued with sodium nitroprusside. A critical discussion is presented in this connection on drugs such as clonidine and reserpine, which reduce pressure largely by central mechanisms and should no longer be applied in pregnant patients because of serious disadvantages. Consideration is also given to the special clinical problems associated with pheochromocytomas, and a concluding discussion deals with the perspectives of antihypertensive therapy in pregnancy. PMID:2053378

  16. Pharmacological effects of Eugenia uniflora (Myrtaceae) aqueous crude extract on rat's heart.

    PubMed

    Consolini, Alicia E; Sarubbio, Marisol Gracía

    2002-06-01

    The effect of aqueous crude extract (ACE) of Eugenia uniflora L. (Myrtaceae) was studied on rat's perfused ventricles. This plant is used in South American traditional medicine as an antihypertensive and we already demonstrated previously its hypotensive properties. In this paper, maximal left intraventriclular pressure (P) of rat's hearts beating at 0.2 Hz firstly increased to 162.1+/-11.1% of basal value during 1-3 min of perfusing ACE 0.6%. Maximum rate of contraction (+P) also increased to duplicating +P/P ratio. Both types of effect were significantly decreased by either propranolol 0.35 microM, and pre-treatment with reserpine (5 mg/kg), suggesting that they were caused by a compound that releases cathecolamines with beta-adrenergic action. Nevertheless, after 20 min of perfusing ACE, ventricles decreased P to about 50% of their basal value, suggesting a negative-inotropic compound present in the extract. The perfusion of 1.2% ACE decreased P in a pressure-[Ca](o) curve (0.5-2 mM) in a non-competitive manner, suggesting that an irreversible Ca-blocking compound is also present in the extract. In summary, E. uniflora ACE has a dual effect on the heart related to its hypotensive action and is probably responsible for the therapeutic or adverse effects in patients under cardiac risk. PMID:12020928

  17. Mutant prevention concentrations of fluoroquinolones against Campylobacter jejuni isolated from chicken.

    PubMed

    Wang, Liping; Yuanshu, Zhang; Yuhan, Zhang; Yaojie; Yingxia, Li

    2010-08-26

    The mutant prevention concentration (MPC) and mutant selection window (MSW) concepts have been used to evaluate antibiotic concentration ranges that prevent the emergence of antibiotic resistant mutants. Campylobacter jejuni is highly mutable to fluoroquinolone (FQ) antibiotics, but it is unknown if the MPC concept can be used to prevent mutant emergence. In this study, the MPCs of three FQs including enrofloxacin, norfloxacin and ciprofloxacin were determined using 13 C. jejuni isolates. Also, first- and second-step FQ-resistant mutants were selected and the mutations in gyrA and gyrB as well as the contribution of efflux pump to FQ resistance were investigated. The MICs of all selected mutants were determined in the presence or absence of the efflux pump inhibitors carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and reserpine. Our results revealed that the three tested FQs had different MPC ranges and the MPC order was norfloxacin > ciprofloxacin > enrofloxacin, suggesting a better in vitro efficacy of enrofloxacin over ciprofloxacin and norfloxacin in reducing the emergence of C. jejuni mutants. The results also confirmed the single-step mechanism of acquired FQs resistance in C. jejuni mutants. Both point mutations (Thr-86-Ile and Asp-90-Asn) in the gyrA gene and the function of efflux pumps contributed to the acquired resistance to ciprofloxacin and norfloxacin, while gyrA mutations (Thr-86-Ile and Asp-90-Asn) were the main mechanism for enrofloxacin resistance. These findings provide new insights into the development and mechanisms of FQ resistance in Campylobacter. PMID:20226601

  18. A method for comparative metabolomics in urine using high resolution mass spectrometry.

    PubMed

    Ramakrishnan, Padma; Nair, Sreenath; Rangiah, Kannan

    2016-04-22

    Developing a workflow for metabolite profiling from biological fluids using mass spectrometry is imperative to extract accurate information. In this study, urine samples from smokers (n=10) and nonsmokers (n=10) were analyzed using an ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) system. For the analysis, two different chromatographic methods [Reversed phase chromatography (RPC) and Hydrophilic interaction liquid chromatography (HILIC)], in two ionization modes (positive and negative) were used. Spiked reserpine (positive ion mode) or taurocholate (negative ion mode) were used for data extraction and normalization. Quality controls (QCs), prepared by pooling urine samples from both smokers and non-smokers (each n=10), were used to assess the reproducibility of the method. The final data output from SIEVE 2.2 after applying a cut-off for QC coefficient of variation (CV) <20% and p-value <0.05 showed 165, 83, 177 and 100 unique components in RP positive/negative, HILIC positive/negative modes, respectively. Statistical analysis showed clustering of the two groups and the QCs, while the variable importance in projection (VIP) scores for the top fifteen metabolites in each of the four modes indicated the metabolites most responsible for the differences. Application of the developed workflow for comparative metabolomic analysis of urine in different diseased models will be of great use in the field of clinical metabolomics. PMID:27012786

  19. Molecular analysis of type II topoisomerases of Aeromonas hydrophila isolated from fish and levofloxacin-induced resistant isolates in vitro.

    PubMed

    Hu, Ruixue; Du, Na; Chen, Nan; Lin, Li; Zhai, Yanhua; Gu, Zemao

    2016-05-01

    The mechanisms of resistance to levofloxacin for Aeromonas hydrophila isolated from diseased fish and selected in vitro were examined in this study. Levofloxacin-resistant mutants were obtained by selection of A. hydrophila in vitro. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were sequenced in Lev(R) strains and reverse mutation strains. All Lev(R) strains carried a point mutation at codon 83 (Ser → Ile), and one strain (25 %) harbored a mutation at position 92 (Leu → Met) in the GyrA-QRDR. After being transferred in a levofloxacin-free medium, one strain of the mutants was successfully reversed and the reversion was related with mutations of GyrA-QRDR at positions 81 (Gly → Asp) and 83 (Ile → Ser). No amino acid alteration was found in the ParC-QRDR. In addition, the minimum inhibitory concentration (MIC) of levofloxacin for the mutants was lower in the presence of reserpine, and all mutants were also resistant to some of the other quinolones. It was found that the mechanism of levofloxacin resistance of A. hydrophila selected in vitro was related to gyrA of type II topoisomerase, and an efflux mechanism was involved in the resistance as well. PMID:26503714

  20. Four pioneers of L-dopa treatment: Arvid Carlsson, Oleh Hornykiewicz, George Cotzias, and Melvin Yahr.

    PubMed

    Lees, Andrew J; Tolosa, Eduardo; Olanow, C Warren

    2015-01-01

    Four individuals stand out as pioneers of the early work that led to levodopa becoming a revolutionary new treatment for Parkinson's disease: Arvid Carlsson, Oleh Hornykiewicz, George C. Cotzias, and Melvin D. Yahr. All four were MDs. The first three had extra training in pharmacology, and in fact did their research in pharmacology. The fourth was a clinical neurologist, the only one in this group with those credentials. The story starts with Carlsson, who became interested in studying the mechanism of reserpine's sedative effect, now recognized as a drug-induced parkinsonian state. A key experiment in 1957 showed that levodopa (l-dopa) could alleviate the immobility induced by reserpine in animals. Carlsson then showed that reserpine depleted brain dopamine, and that l-dopa restored it. Carlsson developed a sensitive fluorescent technique to measure dopamine levels, and his laboratory also showed the distribution of dopamine in animal brain to be highest in the striatum. Within a year, Carlsson postulated that dopamine appears to play a role in motor function. His proposal that dopamine serves as a neurotransmitter in brain was met with much skepticism, but he persisted and continued to study brain dopamine, eventually leading to being awarded the Nobel Prize in Medicine in 2000. Hornykiewicz also went into pharmacology research after graduating from medical school. Fortuitously, his assigned first project was on the blood pressure effects of dopamine, recognized as a precursor of norepinephrine. When he completed his postdoctoral studies, Carlsson's work on the reserpinized animal and on the regional distribution of brain dopamine was published. This inspired Hornykiewicz to determine dopamine levels in patients with Parkinson's disease. He obtained postmortem material, and his 1960 paper showed a marked depletion of dopamine in the striatum in this disorder. He went on in subsequent papers to correlate severity of parkinsonian features with the amount of

  1. The adrenergic-neurone blocking action of some coumaran compounds

    PubMed Central

    Fielden, R.; Roe, A. M.; Willey, G. L.

    1964-01-01

    Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed. PMID:14256809

  2. Characteristics of Ion Activation and Collision Induced Dissociation Using Digital Ion Trap Technology

    NASA Astrophysics Data System (ADS)

    Xu, Fuxing; Dang, Qiankun; Dai, Xinhua; Fang, Xiang; Wang, Yuanyuan; Ding, Li; Ding, Chuan-Fan

    2016-05-01

    Collision induced dissociation (CID) is one of the most established techniques for tandem mass spectrometry analysis. The CID of mass selected ion could be realized by ion resonance excitation with a digital rectangular waveform. The method is simple, and highly efficient CID result could be obtained by optimizing the experimental parameters, such as digital waveform voltage, frequency, and q value. In this work, the relationship between ion trapping waveform voltage and frequency at preselected q value, the relationship between waveform frequency and the q value at certain ion trapping voltage for optimum CID efficiency were investigated. Experiment results showed that the max CID efficiency of precursor reserpine ions can be obtained at different trapping waveform voltage and frequency when q and β are different. Based on systematic experimental analysis, the optimum experimental conditions for high CID efficiency can be calculated at any selected β or q. By using digital ion trap technology, the CID process and efficient fragmentation of parent ions can be realized by simply changing the trapping waveform amplitude, frequency, and the β values in the digital ion trap mass spectrometry. The technology and method are simple. It has potential use in ion trap mass spectrometry.

  3. Effect of mealing on plasma and brain amino acid, and brain monoamine in rats after oral aspartame.

    PubMed

    Torii, K; Mimura, T; Takasaki, Y; Ichimura, M

    1986-01-01

    Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food. PMID:2940610

  4. An electrodynamic ion funnel interface for greater sensitivity and higher throughput with linear ion trap mass spectrometers

    SciTech Connect

    Page, Jason S.; Tang, Keqi; Smith, Richard D.

    2007-09-01

    An electrospray ionization interface incorporating an electrodynamic ion funnel has been designed and implemented in conjunction with a linear ion trap mass spectrometer (Thermo Electron, LTQ). We found ion transmission to be greatly improved by replacing the standard capillary-skimmer interface with the capillary-ion funnel interface. An infusion study using a serial dilution of a reserpine solution showed that ion injection times to fill the ion trap were reduced by ~90% which resulted in an ~10-fold increase in reported peak intensities. In liquid chromatography (LC)-MS and LC tandem MS (MS/MS) experiments performed using a proteomic sample from the bacterium, Shewanella oneidensis, the ion funnel interface provided an ~7-fold reduction in ion injection (accumulation) times. In a series of LC-MS/MS experiments we found that more dilute S. oneidensis samples provided more peptide and protein identifications when the ion funnel interface was used in place of the standard interface. This improvement was most pronounced at lower sample concentrations, where extended ion accumulation times are required, resulting in an ~2-fold increase in the number of protein identifications. Implementation of the ion funnel interface with a LTQ Fourier transform (FT) MS requiring much greater ion populations resulted in spectrum acquisition times reduced by ~25 to 50%.

  5. Ambient diode laser desorption dielectric barrier discharge ionization mass spectrometry of nonvolatile chemicals.

    PubMed

    Gilbert-López, Bienvenida; Schilling, Michael; Ahlmann, Norman; Michels, Antje; Hayen, Heiko; Molina-Díaz, Antonio; García-Reyes, Juan F; Franzke, Joachim

    2013-03-19

    In this work, the combined use of desorption by a continuous wave near-infrared diode laser and ionization by a dielectric barrier discharge-based probe (laser desorption dielectric barrier discharge ionization mass spectrometry (LD-DBDI-MS)) is presented as an ambient ionization method for the mass spectrometric detection of nonvolatile chemicals on surfaces. A separation of desorption and ionization processes could be verified. The use of the diode laser is motivated by its low cost, ease of use, and small size. To achieve an efficient desorption, the glass substrates are coated at the back side with a black point (target point, where the sample is deposited) in order to absorb the energy offered by the diode laser radiation. Subsequent ionization is accomplished by a helium plasmajet generated in the dielectric barrier discharge source. Examples on the application of this approach are shown in both positive and negative ionization modes. A wide variety of multiclass species with low vapor pressure were tested including pesticides, pharmaceuticals and explosives (reserpine, roxithromycin, propazine, prochloraz, spinosad, ampicillin, dicloxacillin, enrofloxacin, tetracycline, oxytetracycline, erythromycin, spinosad, cyclo-1,3,5,7-tetramethylene tetranitrate (HMX), and cyclo-1,3,5-trimethylene trinitramine (RDX)). A comparative evaluation revealed that the use of the laser is advantageous, compared to just heating the substrate surface. PMID:23419061

  6. Initiation of precocious sexual maturation in the immature rat treated with dehydroepiandrosterone.

    PubMed

    Knudsen, J F; Mahesh, V B

    1975-08-01

    Administration of dehydroepiandrosterone (DHA) to immature female rats on day 27 for 3 days resulted in an increase in uterine weight within 6 h of injection and a surge of FSH, LH and prolactin occurred on day 30 resulting in premature ovulation. Increase in ovarian weight and vaginal patency also occurred on day 30. Ovulations occurred at various times on day 30 and some as late as day 33 and these could be synchronized by the administration of pregnant mare serum gonadotropin (PMSG). The gonadotropin surge resulting in ovulation could be blocked by central nervous system blocking agents like phenobarbital and reserpine. The action of DHA in inducing precocious ovulation appeared to be mediated through conversion to estrogens because DHA and testosterone both of which can be aromatized to estrogens at appropriate dose elvels caused potentiation of the effect of PMSG on the secretion of gonadotropins. They also induced vaginal patency in the castrated immature rat. Dihydrotestosterone, an androgen not aromatized to estrogens did not induce precocious ovulation, vaginal patency or potentiation of the effect of PMSG in the release of gonadotropins. Furthermore, cyanoketone an inhibitor of 3beta-hydroxysteroid dehydrogenase and thus the conversion of DHA to estrogens, prevented vaginal patency and DHA-induced precocious ovulation. PMID:125650

  7. Wild Edible Fruit of Prunus nepalensis Ser. (Steud), a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice

    PubMed Central

    Panja, Sourav; Das, Abhishek; Mandal, Nripendranath

    2015-01-01

    The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud), a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME) exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 30.92 ± 0.40 μg/ml). PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38). On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases. PMID:26633891

  8. Some cocaine-like actions of 3-phenoxypropylguanidine

    PubMed Central

    Bartlet, A. L.

    1962-01-01

    In anaesthetized cats 3-phenoxypropylguanidine caused a contracture of the nictitating membrane, a dilatation of the pupil and a fall followed by a rise in the arterial blood pressure. In spinal preparations of cats the initial fall in blood pressure was usually absent and the rise in blood pressure subsided to a steady level, which was about 10 mm Hg above the initial pressure. The pressor action and the contracture of the nictitating membrane were inhibited by phenoxybenzamine and by previous treatment with reserpine, but were not abolished by adrenalectomy and bretylium. 3-Phenoxypropylguanidine potentiated the actions of adrenaline and noradrenaline, increased the blood glucose concentration of the rabbit and decreased the appetite of the cat. The action of tyramine on the cardiovascular system was inhibited by 3-phenoxypropylguanidine, but the stimulant action of tyramine on the nictitating membrane of the cat was not abolished by this substance. Although 3-phenoxypropylguanidine produced a local anaesthesia of long duration in guinea-pig skin, it failed to anaesthetize the rabbit cornea. The responses to stimulation of the preganglionic cervical sympathetic nerve of the cat and the great auricular nerve of the rabbit ear were not abolished by 3-phenoxypropylguanidine; neither did this substance abolish the nicotinic action of acetylcholine in atropinized cats. Contractions of the rat fundus to tryptamine and 5-hydroxytryptamine were antagonized by 3-phenoxypropylguanidine, but were potentiated by cocaine. PMID:13865441

  9. Liquid Microjunction Surface Sampling Probe Electrospray Mass Spectrometry for Detection of Drugs and Metabolites in Thin Tissue Sections

    SciTech Connect

    Van Berkel, Gary J; Kertesz, Vilmos; Koeplinger, Kenneth A.; Vavek, Marissa; Kong, Ah-Ng Tony

    2008-01-01

    A self-aspirating, liquid micro-junction surface sampling probe/electrospray emitter mass spectrometry system was demonstrated for use in the direct analysis of spotted and dosed drugs and their metabolites in thin tissue sections. Proof-of-principle sampling and analysis directly from tissue without the need for sample preparation was demonstrated first by raster scanning a region on a section of rat liver onto which reserpine was spotted. The mass spectral signal from selected reaction monitoring was used to develop a chemical image of the spotted drug on the tissue. The probe was also used to selectively spot sample areas of sagittal whole mouse body tissue sections that had been dosed orally (90 mg/kg) with R,S-sulforaphane 3 hrs prior to sacrifice. Sulforaphane and its glutathione and N-acetyl cysteine conjugates were monitored with selected reaction monitoring and detected in the stomach and various other tissues from the dosed mouse. No signal for these species was observed in the tissue from a control mouse. The same dosed tissue section was used to illustrate the possibility of obtaining a line scan across the whole body section. In total these results illustrate the potential for rapid screening of the distribution of drugs and metabolites in tissue sections with the micro-liquid junction surface sampling probe/electrospray mass spectrometry approach.

  10. A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe).

    PubMed

    Haniadka, Raghavendra; Saldanha, Elroy; Sunita, Venkatesh; Palatty, Princy L; Fayad, Raja; Baliga, Manjeshwar Shrinath

    2013-06-01

    The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger is an important kitchen spice and also possess a myriad health benefits. The rhizomes have been used since antiquity in the various traditional systems of medicine to treat arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, hypertension, dementia, fever, infectious diseases, catarrh, nervous diseases, gingivitis, toothache, asthma, stroke and diabetes. Ginger is also used as home remedy and is of immense value in treating various gastric ailments like constipation, dyspepsia, belching, bloating, gastritis, epigastric discomfort, gastric ulcerations, indigestion, nausea and vomiting and scientific studies have validated the ethnomedicinal uses. Ginger is also shown to be effective in preventing gastric ulcers induced by nonsteroidal anti-inflammatory drugs [NSAIDs like indomethacin, aspirin], reserpine, ethanol, stress (hypothermic and swimming), acetic acid and Helicobacter pylori-induced gastric ulcerations in laboratory animals. Various preclinical and clinical studies have also shown ginger to possess anti-emetic effects against different emetogenic stimuli. However, conflicting reports especially in the prevention of chemotherapy-induced nausea and vomiting and motion sickness prevent us from drawing any firm conclusion on its effectiveness as a broad spectrum anti-emetic. Ginger has been shown to possess free radical scavenging, antioxidant; inhibition of lipid peroxidation and that these properties might have contributed to the observed gastroprotective effects. This review summarizes the various gastroprotective effects of ginger and also emphasizes on aspects that warranty future research to establish its activity and utility as a gastroprotective agent in humans. PMID:23612703

  11. Influence of the beta-adrenergic receptor concentration on functional coupling to the adenylate cyclase system.

    PubMed Central

    Severne, Y; Coppens, D; Bottari, S; Riviere, M; Kram, R; Vauquelin, G

    1984-01-01

    Only part of the beta-adrenergic receptors can undergo functional coupling to the adenylate cyclase regulatory unit. This receptor subpopulation shows an increased affinity for agonists in the presence of Mg2+ and undergoes rapid "inactivation" (locking-in of the agonist) by the alkylating reagent N-ethylmaleimide in the presence of agonists. Several experimental conditions, known to modify the total receptor concentration without alteration of the other components of the adenylate cyclase system, do not affect the percentage of receptors that can undergo functional coupling: (i) homologous regulation of beta 1 receptors in rat brain by noradrenaline (through antidepressive drug or reserpine injections); (ii) up- and down-regulation of the beta 2 receptors in Friend erythroleukemia cells by, respectively, sodium butyrate and cinnarizine treatment; and (iii) dithiothreitol-mediated inactivation of receptors in turkey erythrocytes, Friend erythroleukemia cells, and rat brain. Our findings argue against a stoichiometric limitation in the number of regulatory components, genetically different receptor subpopulations, bound guanine nucleotides, or reduced accessibility of part of the receptors to the agonists as the cause for functional receptor heterogeneity. Differences in either the receptor conformation or its membrane microenvironment are more plausible explanations. PMID:6087337

  12. Treatment resistant depression or dementia: a case report

    PubMed Central

    SHI, Zhongyong; XIAO, Shifu; LI, Xia

    2016-01-01

    Summary: The current case describes a 78-year-old female with two previous episodes of major depression who presented with both symptoms of depression (amotivation and flattened affect) and typical symptoms of dementia (impaired memory and executive functioning). Even after a detailed clinical exam and neuropsychiatric testing, it remained difficult to definitively classify the diagnosis as either treatment-resistant depression or old-age dementia. After 8 weeks of inpatient treatment, including changing her reserpine-based antihypertensive medication, adjusting her antidepressants, and providing psychotherapy, her depressive and anxiety symptoms improved, but most of her cognitive symptoms persisted. Her symptoms did not change over 7 months of post-hospitalization follow-up. She subsequently developed advanced breast cancer and started chemotherapy; at this point her depressive and cognitive symptoms became more pronounced. We conclude that it will take two-to-three years of follow-up to determine whether the cognitive symptoms are residual to her depression or a newly emerging dementia (or both). This case shows that for elderly patients who have symptoms of both depression and dementia, detailed clinical examination and neuropsychiatric testing may need to be combined with longitudinal assessment of their responsiveness to treatment before a definitive diagnosis can be assigned. PMID:27605868

  13. Self-Aspirated Atmospheric Pressure Chemical Ionization Source for Direct Sampling of Analytes on Surfaces and in Liquid Solutions

    SciTech Connect

    Asano, Keiji G; Ford, Michael J; Tomkins, Bruce A; Van Berkel, Gary J

    2005-01-01

    A self-aspirating heated nebulizer probe is described and demonstrated for use in the direct analysis of analytes on surfaces and in liquid samples by atmospheric pressure chemical ionization (APCI) mass spectrometry. Functionality and performance of the probe as a self-aspirating APCI source is demonstrated using reserpine and progesterone as test compounds. The utility of the probe to sample analytes directly from surfaces was demonstrated first by scanning development lanes of a reversed-phase thin-layer chromatography plate in which a three-component dye mixture, viz., Fat Red 7B, Solvent Green 3, and Solvent Blue 35, was spotted and the components were separated. Development lanes were scanned by the sampling probe operated under computer control (x, y plane) while full-scan mass spectra were recorded using a quadrupole ion trap mass spectrometer. In addition, the ability to sample the surface of pharmaceutical tablets (viz., Extra Strength Tylenol(reg. sign) and Evista(reg. sign) tablets) and to detect the active ingredients (acetaminophen and raloxifene, respectively) selectively was demonstrated using tandem mass spectrometry (MS/MS). Finally, the capability to sample analyte solutions from the wells of a 384-well microtiter plate and to perform quantitative analyses using MS/MS detection was illustrated with cotinine standards spiked with cotinine-d{sub 3} as an internal standard.

  14. Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells

    SciTech Connect

    Smets, L.A.; Loesberg, C.; Janssen, M.; Metwally, E.A.; Huiskamp, R.

    1989-06-01

    Radioiodinated m-iodobenzylguanidine (MIBG), an analogue of the neurotransmitter norepinephrine (NE), is increasingly used in the diagnosis and treatment of neural crest tumors. Active uptake and subsequent retention of MIBG and NE was studied in human neuroblastoma SK-N-SH cells. Neuron-specific uptake of (125I)MIBG and (3H)NE saturated at extracellular concentration of 10(-6) M and exceeded by 20-30-fold that by passive diffusion alone. A minimum of 50% of accumulated MIBG remained permanently stored but the SK-N-SH cells were incapable of retaining recaptured (3H)NE. (125I)MIBG was displaced from intracellular binding sites by unlabeled MIBG with 10-fold higher potency than by unlabeled NE. MIBG stored in SK-N-SH cells was insensitive to depletion by the inhibitor of granular uptake reserpine (RSP) and was not precipitated in a granular fraction by differential centrifugation. Only few electron-dense granules were found in these cells by electron microscopy. In contrast, MIBG storage in PC-12 pheochromocytoma cells which contained many storage granules, was sensitive to RSP and part of accumulated drug was recovered in a granular fraction. Accordingly, storage of MIBG in the SK-N-SH neuroblastoma cells is predominantly extravesicular and thus essentially different from that of biogenic amines in normal adrenomedullary tissue or in pheochromocytoma tumors, while sharing with these tissues a common mechanism of active uptake.

  15. Effects and underlying mechanisms of human opiorphin on cardiovascular activity in anesthetized rats.

    PubMed

    Tian, Xiao-zhu; Chen, Yong; Bai, Lu; Luo, Pan; Du, Xue-jing; Chen, Qiang; Tian, Xin-min

    2015-02-15

    The present study was performed to investigate the peripheral cardiovascular effects of opiorphin in anesthetized rats. Intravenous (i.v.) injection of opiorphin (50-500nmol/kg) caused marked dose-dependent increase in blood pressure and heart rate. The pressor and tachycardic responses induced by opiorphin (300nmol/kg, i.v.) were significantly decreased by pretreatment with angiotensin-converting enzyme inhibitor captopril or angiotensin II type 1 (AT1) receptor antagonist valsartan, which suggested that endogenous angiotensin may be involved in the response to opiorphin. Pretreatment with α-adrenoreceptor antagonist phentolamine and β-adrenoceptor antagonist propranolol respectively attenuated the pressor response induced by opiorphin. Propranolol, but not phentolamine, inhibited the tachycardic response. Moreover, reserpine blocked both responses to opiorphin. These findings indicated that the effects of opiorphin to increase blood pressure and heart rate might be due to the stimulation of sympathetic ganglia. Additionally, studies with bilaterally adrenalectomized rats showed that adrenal medulla may be involved in the cardiovascular regulation of opiorphin. In addition, pretreatment with nonselective opioid receptor antagonist naloxone did not modify the cardiovascular responses to opiorphin, suggesting that the effects of opiorphin were not related to the opioid system. Furthermore, radioimmunoassay (RIA) showed that opiorphin significantly increased endogenous levels of angiotensin II and angiotensin III. In summary, all the results indicate that the cardiovascular effects induced by opiorphin are mediated through the renin-angiotensin system (RAS), the sympathetic ganglia and adrenal medulla, but not the opioid system. PMID:25460028

  16. Initial experimental characterization of a new ultra-high resolution FTICR cell with dynamic harmonization.

    PubMed

    Nikolaev, Eugene N; Boldin, Ivan A; Jertz, Roland; Baykut, Gökhan

    2011-07-01

    A new Fourier transform ion cyclotron resonance (FTICR) cell based on completely new principles of formation of the effective electric potential distribution in Penning type traps, Boldin and Nikolaev (Proceedings of the 58th ASMS Conference, 2010), Boldin and Nikolaev (Rapid Commun Mass Spectrom 25:122-126, 2011) is constructed and tested experimentally. Its operation is based on the concept of electric potential space-averaging via charged particle cyclotron motion. Such an averaging process permits an effective electric force distribution in the entire volume of a cylindrical Penning trap to be equal to its distribution in the field created by hyperbolic electrodes in an ideal Penning trap. The excitation and detection electrodes of this new cell are shaped for generating a quadratic dependence on axial coordinates of an averaged (along cyclotron motion orbit) electric potential at any radius of the cyclotron motion. These electrodes together with the trapping segments form a cylindrical surface like in a conventional cylindrical cell. In excitation mode this cell being elongated behaves almost like an open cylindrical cell of the same length. It is more effective in ion motion harmonization at larger cyclotron radii than a Gabrielse et al.-type (Int J Mass Spectrom Ion Processes 88:319-332, 1989) cylindrical cell with four compensation sections. A mass resolving power of more than twenty millions of reserpine (m/z 609) and more than one million of highly charged BSA molecular ions (m/z 1357) has been obtained in a 7T magnetic field. PMID:21953094

  17. Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry.

    PubMed

    Nemes, Peter; Vertes, Akos

    2007-11-01

    Mass spectrometric analysis of biomolecules under ambient conditions promises to enable the in vivo investigation of diverse biochemical changes in organisms with high specificity. Here we report on a novel combination of infrared laser ablation with electrospray ionization (LAESI) as an ambient ion source for mass spectrometry. As a result of the interactions between the ablation plume and the spray, LAESI accomplishes electrospray-like ionization. Without any sample preparation or pretreatment, this technique was capable of detecting a variety of molecular classes and size ranges (up to 66 kDa) with a detection limit of 8 and 25 fmol for verapamil and reserpine, respectively, and quantitation capabilities with a four-decade dynamic range. We demonstrated the utility of LAESI in a broad variety of applications ranging from plant biology to clinical analysis. Proteins, lipids, and metabolites were identified, and antihistamine excretion was followed via the direct analysis of bodily fluids (urine, blood, and serum). We also performed in vivo spatial profiling (on leaf, stem, and root) of metabolites in a French marigold (Tagetes patula) seedling. PMID:17900146

  18. Minimizing analyte electrolysis in electrospray ionization mass spectrometry using a redox buffer coated emitter electrode

    SciTech Connect

    Peintler-Krivan, Emese; Van Berkel, Gary J; Kertesz, Vilmos

    2010-01-01

    An emitter electrode with an electroactive poly(pyrrole) (PPy) polymer film coating was constructed for use in electrospray ionization mass spectrometry (ESI-MS). The PPy film acted as a surface-attached redox buffer limiting the interfacial potential of the emitter electrode. While extensive oxidation of selected analytes (reserpine and amodiaquine) was observed in positive ion mode ESI using a bare metal (gold) emitter electrode, the oxidation was suppressed for these same analytes when using the PPy-coated electrode. A semi-quantitative relationship between the rate of oxidation observed and the interfacial potential of the emitter electrode was shown. The redox buffer capacity, and therefore the lifetime of the redox buffering effect, correlated with the oxidation potential of the analyte and with the magnitude of the film charge capacity. Online reduction of the PPy polymer layer using negative ion mode ESI between analyte injections was shown to successfully restore the redox buffering capacity of the polymer film to its initial state.

  19. The effects of paraoxon on blood pressure in the anaesthetized and in the conscious rat

    PubMed Central

    de Neef, J.H.; Jordaan, K.M.; Porsius, A.J.

    1982-01-01

    1 Intravenous administration of paraoxon (150-825 μg/kg) to anaesthetized rats induced long-lasting, dose-dependent pressor effects. Only after injection of 825 μg/kg paraoxon was the pressor response followed by a depressor effect and a bradycardia that could be blocked by N-methylatropine. Intracerebroventricular injection of paraoxon into anaesthetized rats also induced pressor effects. 2 In order to elucidate the mechanism of the pressor action rats were given dexetimide, N-methylatropine, mecamylamine, phentolamine, prazosin, yohimbine, atenolol and metoprolol. If treatment with these drugs resulted in a low initial blood pressure, vasopressin was infused to elevate blood pressure to normal levels. The influence of adrenalectomy, pretreatment with reserpine and midcollicular transection was also examined. 3 The pressor effect of paraoxon was not influenced by N-methylatropine or mecamylamine. However, a combination of these drugs as well as dexetimide, phentolamine or prazosin combined with yohimbine, reduced or prevented the pressor effect. 4 In conscious rats the effects of paraoxon and the action of antimuscarinic drugs upon the pressor response were similar to those observed in anaesthetized animals. 5 Acetylcholinesterase activities were measured in various brain regions and in whole blood. Paraoxon concentrations within the CNS were also measured. 6 It is concluded that the pressor effect of paraoxon in anaesthetized and conscious rats is mediated by a central mechanism, although a contribution of peripheral acetylcholinesterase inhibition in sympathetic ganglia to this pressor effect cannot be ruled out. PMID:7139183

  20. Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species: possible role for drug efflux in drug resistance.

    PubMed Central

    Clark, F S; Parkinson, T; Hitchcock, C A; Gow, N A

    1996-01-01

    A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell. We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part to active drug efflux. Rhodamine 123 (Rh123) is a fluorescent compound that is transported by a wide variety of MDR cell types. We have shown that certain azole-resistant strains of Candida albicans, C. glabrata, and C. krusei accumulate less Rh123 than azole-susceptible ones. In C. albicans, Rh123 accumulation was growth phase and temperature dependent and was increased by proton uncouplers and by reserpine, an MDR modulator. This is consistent with an energy-dependent efflux mechanism for Rh123, mediated by an MDR transporter. In C. glabrata, but not in C. albicans, there was competition between Rh123 and fluconazole for efflux. Thus, in C. glabrata, Rh123 and fluconazole appear to be transported via a common MDR-like transporter, whereas in C. albicans, the Rh123 transporter does not appear to transport azoles. PMID:8834890

  1. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    SciTech Connect

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J. )

    1990-05-01

    Sites of uptake, storage, and metabolism of ({sup 18}F)fluorodopamine and excretion of ({sup 18}F)fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of ({sup 18}F)-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of ({sup 18}F)fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

  2. Contractile effect of vanadate and other vanadium compounds on the rat vas deferens.

    PubMed

    Garcia, A G; Jurkiewicz, A; Jurkiewicz, N H

    1981-03-01

    Sodium metavanadate (NaVO3), vanadium pentoxide (V2O5) and vanadyl sulphate (VOSO4), evoked rhythmic and tonic contractions of the normal and reserpinized rat isolated vas deferens. Contractions were not observed by the use of vanadium trichloride (VCl3) The order of potency of these compounds, for their maximum contractile effects was NaVO3 greater than V2O5 greater than VOSO4 greater than VCl3. Differences in pD2 values were less than 0.5 long units in relation to the first compound. Vanadium-induced contractions were blocked by Ca2+ deprivation, nifedipine, Mg2+, Mn2+, Ni2+ and Co2+, indicating the involvement of a loosely bound or extracellular calcium-dependent mechanism. It is still unclear whether this calcium translocation was related, or not, to changes in Na+, K+-ATPase activity. Since ouabain blocked the action of vanadyl or vanadate non-competitively, it is concluded that vanadium compounds and ouabain induce their effects by interacting with different sites in vas deferens, both of which may or may not be located on the (Na+, K+)ATPase enzyme complex. PMID:6908559

  3. Characteristics of Ion Activation and Collision Induced Dissociation Using Digital Ion Trap Technology.

    PubMed

    Xu, Fuxing; Dang, Qiankun; Dai, Xinhua; Fang, Xiang; Wang, Yuanyuan; Ding, Li; Ding, Chuan-Fan

    2016-08-01

    Collision induced dissociation (CID) is one of the most established techniques for tandem mass spectrometry analysis. The CID of mass selected ion could be realized by ion resonance excitation with a digital rectangular waveform. The method is simple, and highly efficient CID result could be obtained by optimizing the experimental parameters, such as digital waveform voltage, frequency, and q value. In this work, the relationship between ion trapping waveform voltage and frequency at preselected q value, the relationship between waveform frequency and the q value at certain ion trapping voltage for optimum CID efficiency were investigated. Experiment results showed that the max CID efficiency of precursor reserpine ions can be obtained at different trapping waveform voltage and frequency when q and β are different. Based on systematic experimental analysis, the optimum experimental conditions for high CID efficiency can be calculated at any selected β or q. By using digital ion trap technology, the CID process and efficient fragmentation of parent ions can be realized by simply changing the trapping waveform amplitude, frequency, and the β values in the digital ion trap mass spectrometry. The technology and method are simple. It has potential use in ion trap mass spectrometry. Graphical Abstract ᅟ. PMID:27150507

  4. Tissue specific regulation of peripheral-type benzodiazepine receptor density after chemical sympathectomy

    SciTech Connect

    Basile, A.S.; Skolnick, P.

    1988-01-01

    The characteristics of (/sup 3/H)Ro 5-4864 binding to peripheral benzodiazepine receptors (PBR) in the central nervous system and peripheral tissues were examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA). One week after the intracisternal administration of 6-OHDA, the number of (/sup 3/H)Ro 5-4864 binding sites (Bmax) in the hypothalamus and striatum increased 41 and 50% respectively, concurrent with significant reductions in catecholamine content. An increase (34%) in the Bmax of (/sup 3/H)Ro 5-4864 to cardiac ventricle was observed one week after parenteral 6-OHDA administration. In contrast, the B/sub max/ of (/sup 3/H)Ro 5-4684 to pineal gland decreased 48% after 6-OHDA induced reduction in norepinephrine content. The Bmax values for (/sup 3/H)Ro 5-4864 binding to other tissues (including lung, kidney, spleen, cerebral cortex, cerebellum, hippocampus and olfactory bulbs) were unaffected by 6-OHDA administration. The density of pineal, but not cardiac PBR was also reduced after reserpine treatment, an effect reversed by isoproterenol administration. These findings demonstrate that alterations in sympathetic input may regulate the density of PBR in both the central nervous system and periphery in a tissue specific fashion. 33 references, 4 tables.

  5. Requirements for laser-induced desorption/ionization on submicrometer structures.

    PubMed

    Okuno, Shoji; Arakawa, Ryuichi; Okamoto, Kazumasa; Matsui, Yoshinori; Seki, Shu; Kozawa, Takahiro; Tagawa, Seiichi; Wada, Yoshinao

    2005-08-15

    Laser-induced and matrix-free desorption/ionization on various submicrometer structures was investigated. First, to examine the effect of surface roughness on ionization, a silicon wafer or stainless steel was scratched with sandpaper. The fluences of a 337-nm nitrogen laser, required for ionization of synthetic polymers and reserpine, were markedly reduced on the scratched stainless steel or silicon as compared to the corresponding untreated surface. Next, arrays of submicrometer grooves, which had been lithographically fabricated on a silicon wafer, yielded protonated angiotensin, and the morphologic orientation demonstrated the positive relation between the laser and groove directions for promoting ionization. The fabricated structure also suggested the submicrometer, but not smaller, or nanometer, structures to be a key factor in direct desorption/ionization on rough surfaces. Finally, submicrometer porous structures of alumina or polyethylene yielded intense molecular ion signals of angiotensin and insulin, in response to direct UV irradiation, when the surface was coated with Au or Pt. The coating provided the additional advantage of prolonged activity for a porous alumina chip, exceeding a month even when the chip was left in the open air. These results indicate that laser-induced desorption/ionization of organic compounds can be implemented on submicrometer structures with an Au- or Pt-coated surface irrespective of the basal materials. PMID:16097781

  6. Identification of a mammalian vesicular polyamine transporter

    PubMed Central

    Hiasa, Miki; Miyaji, Takaaki; Haruna, Yuka; Takeuchi, Tomoya; Harada, Yuika; Moriyama, Sawako; Yamamoto, Akitsugu; Omote, Hiroshi; Moriyama, Yoshinori

    2014-01-01

    Spermine and spermidine act as neuromodulators upon binding to the extracellular site(s) of various ionotropic receptors, such as N-methyl-d-aspartate receptors. To gain access to the receptors, polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Although vesicular storage is mediated in an ATP-dependent, reserpine-sensitive fashion, the transporter responsible for this process remains unknown. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine by exchange of H+. SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes. These results indicated that SLC18B1 encodes a vesicular polyamine transporter (VPAT). PMID:25355561

  7. Treatment resistant depression or dementia: a case report.

    PubMed

    Shi, Zhongyong; Xiao, Shifu; Li, Xia

    2016-04-25

    The current case describes a 78-year-old female with two previous episodes of major depression who presented with both symptoms of depression (amotivation and flattened affect) and typical symptoms of dementia (impaired memory and executive functioning). Even after a detailed clinical exam and neuropsychiatric testing, it remained difficult to definitively classify the diagnosis as either treatment-resistant depression or old-age dementia. After 8 weeks of inpatient treatment, including changing her reserpine-based antihypertensive medication, adjusting her antidepressants, and providing psychotherapy, her depressive and anxiety symptoms improved, but most of her cognitive symptoms persisted. Her symptoms did not change over 7 months of post-hospitalization follow-up. She subsequently developed advanced breast cancer and started chemotherapy; at this point her depressive and cognitive symptoms became more pronounced. We conclude that it will take two-to-three years of follow-up to determine whether the cognitive symptoms are residual to her depression or a newly emerging dementia (or both). This case shows that for elderly patients who have symptoms of both depression and dementia, detailed clinical examination and neuropsychiatric testing may need to be combined with longitudinal assessment of their responsiveness to treatment before a definitive diagnosis can be assigned. PMID:27605868

  8. An electrodynamic ion funnel interface for greater sensitivity and higher throughput with linear ion trap mass spectrometers

    NASA Astrophysics Data System (ADS)

    Page, Jason S.; Tang, Keqi; Smith, Richard D.

    2007-09-01

    An electrospray ionization interface incorporating an electrodynamic ion funnel has been designed and implemented on a linear ion trap mass spectrometer (Thermo Electron, LTQ). We found ion transmission to be greatly improved by replacing the standard capillary-skimmer interface with the capillary-ion funnel interface. An infusion study using a serial dilution of a reserpine solution showed that ion injection (accumulation) times to fill the ion trap at a given automatic gain control (AGC) target value were reduced by ~90% which resulted in an ~10-fold increase in peak intensities. In liquid chromatography tandem MS (LC-MS/MS) experiments performed using a global protein digest sample from the bacterium, Shewanella oneidensis, more peptides and proteins were identified when the ion funnel interface was used in place of the standard interface. This improvement was most pronounced at lower sample concentrations, where extended ion accumulation times are required, resulting in an ~2-fold increase in the number of protein identifications. Implementation of the ion funnel interface on a LTQ Fourier transform (FT) mass spectrometer showed a ~25-50% reduction in spectrum acquisition time. The duty cycle improvement in this case was due to the ion accumulation event contributing a larger portion to the total spectrum acquisition time.

  9. Neurotoxic compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) depletes endogenous norepinephrine and enhances release of (/sup 3/H)norepinephrine from rat cortical slices

    SciTech Connect

    Landa, M.E.; Rubio, M.C.; Jaim-Etcheverry, G.

    1984-10-01

    The alkylating compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) injected to rodents blocks norepinephrine (NE) uptake and reduces endogenous NE levels in the central nervous system and in the periphery. To investigate the processes leading to these alterations, rat cortical slices were incubated in the presence of DSP4. Cortical NE was depleted by 40% after incubation of slices in 10(-5) M DSP4 for 60 min and this was blocked by desipramine. The spontaneous outflow of radioactivity from cortical slices labeled previously with (/sup 3/H)NE was enhanced markedly both during exposure to DSP4 and during the subsequent washings, suggesting that NE depletion could be due to this stimulation of NE release. The radioactivity released by DSP4 was accounted for mainly by NE and its deaminated metabolite 3,4-dihydroxyphenylglycol. The enhanced release, independent of external Ca++, apparently originated from the vesicular pool as it was absent after reserpine pretreatment. Activities of the enzymes related to NE synthesis were not altered by DSP4 in vitro and only monoamine oxidase activity was inhibited at high concentrations. Thus, the depletion of endogenous NE produced by DSP4 is probably due to a persistent enhancement of its release from the vesicular pool. Fixation of DSP4 to the NE transport system is necessary but not sufficient to produce the acute NE depletion and the characteristic long-term actions of the compound.

  10. 5-Hydroxytryptamine release from platelets by different red wines: implications for migraine.

    PubMed

    Pattichis, K; Louca, L L; Jarman, J; Sandler, M; Glover, V

    1995-01-13

    We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high correlation (r = 0.87) between the effect of red wine and that of reserpine in different individuals. Some types of red wine caused a consistently higher release of 5-HT than others in all subjects; one red wine in particular resulted in negligible release. When several brands of this 'low-releasing' red wine were further examined, they all showed a lower activity than all the brands of a 'high-releasing' red wine type. This variation in releasing power was not related to intensity of red colour. Partial purification of red wine was achieved by column chromatography and showed releasing activity to be associated with a low molecular weight orange fraction. Preliminary studies, using solid phase extraction methods, showed that the active components lie mainly in a subgroup of the flavonoid fraction. If any of the adverse effects of red wine, such as headache induction, derive from this 5-HT releasing ability, then it may be possible to prepare red wines free from the chemical substances responsible. PMID:7720790

  11. Characteristics of Ion Activation and Collision Induced Dissociation Using Digital Ion Trap Technology

    NASA Astrophysics Data System (ADS)

    Xu, Fuxing; Dang, Qiankun; Dai, Xinhua; Fang, Xiang; Wang, Yuanyuan; Ding, Li; Ding, Chuan-Fan

    2016-08-01

    Collision induced dissociation (CID) is one of the most established techniques for tandem mass spectrometry analysis. The CID of mass selected ion could be realized by ion resonance excitation with a digital rectangular waveform. The method is simple, and highly efficient CID result could be obtained by optimizing the experimental parameters, such as digital waveform voltage, frequency, and q value. In this work, the relationship between ion trapping waveform voltage and frequency at preselected q value, the relationship between waveform frequency and the q value at certain ion trapping voltage for optimum CID efficiency were investigated. Experiment results showed that the max CID efficiency of precursor reserpine ions can be obtained at different trapping waveform voltage and frequency when q and β are different. Based on systematic experimental analysis, the optimum experimental conditions for high CID efficiency can be calculated at any selected β or q. By using digital ion trap technology, the CID process and efficient fragmentation of parent ions can be realized by simply changing the trapping waveform amplitude, frequency, and the β values in the digital ion trap mass spectrometry. The technology and method are simple. It has potential use in ion trap mass spectrometry.

  12. Angiotensin converting enzyme in the brain, testis, epididymis, pituitary gland and adrenal gland

    SciTech Connect

    Strittmatter, S.M.

    1986-01-01

    (/sup 3/H)Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of (/sup 3/H)captopril binding with enzymatic activity demonstrate the selectivity of (/sup 3/H)captopril labeling of ACE. (/sup 3/H)Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. (/sup 3/H)Captopril association with ACE is entropically driven. The selectivity of (/sup 3/H)captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1 and 7 d after birth. In the male reproductive system, (/sup 3/H)captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment. The general of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor (/sup 3/H)GEMSA.

  13. Bovine ovarian follicular cysts: in vitro effects of lecirelin, a GnRH analogue.

    PubMed

    Rizzo, Annalisa; Cosola, Claudia; Mutinati, Maddalena; Spedicato, Massimo; Minoia, Giuseppe; Sciorsci, Raffaele Luigi

    2010-12-01

    This study investigates the mechanisms of action by which a GnRH analogue may modulate the contractility of the bovine ovarian follicular wall. The in vitro evaluation of the spontaneous basal contractility of bovine preovulatory and cystic follicles was performed, followed by testing the effects of lecirelin, a GnRH analogue, on their basal contractility. Strips of tissue in isolated organ bath were employed. In addition, to better investigate the mechanism of action of lecirelin, the study of the effects of cumulative doses of nifedipine (a calcium channel blocker), phentolamine (an α-adrenoceptor antagonist) and reserpine (an inhibitor of the vesicular up-take of catecholamines) alone and, at the highest doses employed, associated to lecirelin, was set up. The results demonstrate that in basal conditions and after the addition of lecirelin, the strips from preovulatory follicles contract significantly more than strips from cysts. Furthermore, among the patterns of contractility evoked by the three drugs employed, the one induced by nifedipine was the only one unaffected by the addition of lecirelin. The data obtained provide the hypothesis that one of the main mechanisms of action of GnRH, could involve calcium channels. PMID:20691467

  14. The antidepressant-like effect of bacopaside I: possible involvement of the oxidative stress system and the noradrenergic system.

    PubMed

    Liu, Xiaojun; Liu, Fang; Yue, Rongcai; Li, Yuanyuan; Zhang, Jigang; Wang, Shuping; Zhang, Shoude; Wang, Rui; Shan, Lei; Zhang, Weidong

    2013-09-01

    In the present study, the antidepressant-like effect of bacopaside I, a saponin compound present in the Bacopa monniera plant, was evaluated by behavioral and neurochemical methods. Bacopaside I (50, 15 and 5 mg/kg) was given to mice via oral gavage for 7 successive days. The treatment significantly decreased the immobility time in mouse models of despair tests, but it did not influence locomotor activity. Neurochemical assays suggested that treatment by bacopaside I (50, 15 and 5 mg/kg) improved brain antioxidant activity to varying degrees after the behavioral despair test. Bacopaside I (15 and 5 mg/kg) significantly reversed reserpine-induced depressive-like behaviors, including low temperature and ptosis. Conversely, bacopaside I did not affect either brain MAO-A or MAO-B activity after the behavioral despair test in mice. Additionally, 5-hydroxytryptophan (a precursor of 5-serotonin) was not involved in the antidepressant-like effect of bacopaside I. These findings indicated that the antidepressant-like effect of bacopaside I might be related to both antioxidant activation and noradrenergic activation, although the exact mechanism remains to be further elucidated. PMID:23872136

  15. Central neurotransmitter disturbances underlying developmental neurotoxicological effects.

    PubMed

    Mirmiran, M; Swaab, D F

    1986-01-01

    Transmission of information among neurons is of a chemical nature. The activity of the neurotransmitter in the brain is regulated by the spontaneous activity of neurotransmitter cell body and the sensitivity of both pre- and post-synaptic receptors. Neurotransmitters are present at very early stages of brain development; they do not only mediate the behavioral-physiological responses of the immature animal, but have trophic effects on the maturation of target neurons as well. Many centrally acting drugs which are frequently used also during pregnancy for the treatment of depression, hypertension, epilepsy, asthma, insomnia, hyperkinetism and other neurological and psychiatric disorders act directly on brain neurotransmitters (in particular monoamines) and behavioral states. Chronic administration of drugs acting on monoamines (such as clonidine, imipramine, alpha-methyl-Dopa, reserpine, monoamine oxidase inhibitors, diazepam) disturb the spontaneous activity and behavioral state dependency of the monoaminergic cells, influences neurotransmitter turnover and change the sensitivity of both pre- and post-synaptic receptors. Sensory deprivation during a critical period of development is known to produce permanent effect on the brain; e.g., monocular deprivation during a particular period of development in a kitten leads to a rewiring of the connectivity in the visual system in the adult cat. Disturbances in neurotransmitter activity during early life will induce a comparable reorganization of the chemical structure of the adult brain. PMID:2878401

  16. Neuronal mapping of the heart with 6-( sup 18 F)fluorometaraminol

    SciTech Connect

    Wieland, D.M.; Rosenspire, K.C.; Hutchins, G.D.; Van Dort, M.; Rothley, J.M.; Mislankar, S.G.; Lee, H.T.; Massin, C.C.; Gildersleeve, D.L.; Sherman, P.S. )

    1990-03-01

    The false neurotransmitter metaraminol labeled with fluorine-18 has been used to noninvasively assess regional adrenergic nerve density in the canine heart. Intravenous administration of 6-({sup 18}F)fluorometaraminol (FMR) results in high, selective accumulation of radioactivity in the heart; drug blocking studies with desipramine and reserpine confirm the neuronal locus of FMR. Iodine-125 labeled metaraminol, however, shows no selective accumulation in the canine heart. Positron emission tomography (PET) analyses with FMR of closed-chest dogs bearing left ventricular neuronal defects clearly delineate the region of neuronal impairment; blood perfusion in the left ventricle wall was homogeneous as determined by (13N)NH3 tomograms. The accumulation of FMR in regionally denervated dog heart correlates closely (r = 0.88) with endogenous norepinephrine concentrations. PET-generated 18F time-activity curves demonstrate marked kinetic differences between normal and denervated myocardium. FMR/PET analysis could be used to assess the heterogeneity of sympathetic innervation in human heart disease contingent on the development of FMR with sufficiently high specific activity to clearly avoid pressor activity.

  17. Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa.

    PubMed

    Jürgensen, Sofia; Dalbó, Sílvia; Angers, Paul; Santos, Adair Roberto Soares; Ribeiro-do-Valle, Rosa Maria

    2005-07-01

    Uncaria tomentosa (Willd.) DC (Rubiaceae) is a vine that grows in the Amazon rainforest. Its bark decoctions are used by Peruvian Indians to treat several diseases. Chemically, it consists mainly of oxindole alkaloids. An industrial fraction of U. tomentosa (UT fraction), containing 95% oxindole alkaloids, was used in this study in order to characterize its antinociceptive activity in chemical (acetic acid-induced abdominal writhing, formalin and capsaicin tests) and thermal (tail-flick and hot-plate tests) models of nociception in mice. UT fraction given by the i.p. route dose-dependently suppressed the behavioural response to the chemical stimuli in the models indicated and increased latencies in the thermal stimuli models. The antinociception caused by UT fraction in the formalin test was significantly attenuated by i.p. treatment of mice with ketanserin (5-HT2 receptor antagonist), but was not affected by naltrexone (opioid receptor antagonist), atropine (a nonselective muscarinic antagonist), l-arginine (precursor of nitric oxide), prazosin (alpha1-adrenoceptor antagonist), yohimbine (alpha2-adrenoceptor antagonist), and reserpine (a monoamine depleter). Together, these results indicate that UT fraction produces dose-related antinociception in several models of chemical and thermal pain through mechanisms that involve an interaction with 5-HT2 receptors. PMID:15907989

  18. Effect of the alkaloid (-)cathinone on the release of radioactivity from rabbit atria prelabelled with /sup 3/H-norepinephrine

    SciTech Connect

    Kalix, P.

    1983-02-14

    In certain countries of East Africa and the Arab Peninsula, fresh leaves of the khat shrub are used as a stimulant. The effect of the plant material can be explained by the presence of the phenylalklamine alkaloid (-)cathinone in the leaves, since this substance has been shown to have an amphetamine-like releasing effect on CNS tissue prelabelled with /sup 3/H-dopamine. Characteristically, the chewing of khat is accompanied by sympathomimetic effects, especially at the cardiovascular level. To test whether these might be due to release of neurotransmitter from adrenergic nerve endings, the effect of (-)cathinone on the efflux of radioactivity from isolated rabbit atrium tissue prelabelled with /sup 3/H-norepinephrine was investigated. It was found that, at concentrations below 1 ..mu..M, (-)cathinone caused an immediate increase of efflux. The effect was dose-dependent and was potentiated by pretreatment of the rabbits with reserpine. Preincubation of the tissue with desipramine and cocaine prevented the induction of release by (-)cathinone. The results indicate that the alkaloid (-)cathinone has an amphetamine-like releasing effect on noradrenergic nerve endings and they suggest that the cardiovascular symptoms observed during khat consumption are due to release of neurotransmitter from physiologicl storage sites.

  19. Investigation of the enzymology and pharmacology of novel substrates and inhibitors of dopamine beta-monooxygenase

    SciTech Connect

    Roberts, S.F.

    1987-01-01

    Dopamine beta-monooxygenase (DBM) was shown to catalyze the selenoxidation of 2-(phenylseleno)ethylamines, selenium-containing analogues of dopamine, by the normal monooxygenase pathway. The compounds 2-(phenylseleno)-ethylamine (PAESe), 2-(4'-hydroxyphenylseleno)ethylamine (pOH PAESe), and 1-(phenylseleno)-2-propylamine (Me PAESe) were synthesized and fully characterized as DBM substrates. Two other classes of compounds were investigated as potential alternate substrates for DBM. The possibility of stereoselective sulfonylation of 2-(phenylsulfenyl)- ethylamine (PAESO) was considered. A unique class of compounds, 2-(phenylthio)ethanols were designed and synthesized as DBM substrates but were found to be a novel class of potent competitive inhibitors of DBM with respect to tyramine. Preliminary experiments were also performed in an effort to demonstrate that the potent antihypertensive and indirect-acting sympathomimetic activity of 2-(phenylthio)ethylamine (PAES) was a result of DBM-oxygenation of this compound in vivo. The specific reserpine-sensitive uptake of (/sup 3/H)-norepinephrine into rat brain synaptosomes was demonstrated as was the synaptosomal conversion of (/sup 3/H)-dopamine to (/sup 3/H)-norepinephrine.

  20. Myocardial imaging with a radioiodinated norepinephrine storage analog

    SciTech Connect

    Wieland, D.M.; Brown, L.E.; Rogers, W.L.; Worthington, K.C.; Wu, J.L.; Clinthorne, N.H.; Otto, C.A.; Swanson, D.P.; Beierwaltes, W.H.

    1981-01-01

    Meta-iodobenzylguanidine (M-IBG), an iodinated aromatic analog of the hypotensive drug guanethidine, localizes in the heart of the rat, dog, and rhesus monkey. A comparative study of tissue distribution in the dog has been performed with five myocardiophilic agents: thallium-201, I-125 16-iodohexadecanoic acid, H-3 norepinephrine, C-14 guanethidine and I-125 M-IBG. The last two compounds give heart concentrations and heart-to-blood concentration ratios similar to those of thallium-201. Planar and tomographic images of the hearts of the dog and rhesus monkey were obtained using I-131 or I-123 labeled M-IBG. Blocking studies with reserpine suggest that a major component of myocardial retention of M-IBG is sequestration within the norepinephrine storage vesicles of the adrenergic nerves. The localization of M-IBG in other organs with rich sympathetic innervation and the relative insensitivity of myocardial uptake to a wide range of loading doses lend additional support for a neuronal mode of retention.

  1. [Chemotherapies of negative schizophrenia].

    PubMed

    Petit, M; Dollfus, S

    1991-01-01

    Five years ago, Goldberg claimed that negative symptoms of schizophrenia do respond to neuroleptics. This apparent discovery is, in fact, a very common way of thinking for European schools of psychiatry, specially the French one guided by Delay and Deniker. Initially focused on reserpine and some alerting phenothiazines such as thioproperazine, this opinion has been extended to benzamides in the 1970s. The analysis of the publications devoted to this point indicates that several drugs are actually considered as potent disinhibitors (i.e. active on negative symptoms of schizophrenia): Phenothiazines: As shown in the controlled studies by Itil (1971), Poirier-Littré (1988), fluphenazine and pipotiazine improve the BPRS anergia factor and the SANS score. Butyrophenones: The first description of the "imipramine like" effect of trifluperidol by Janssen (1959) initiated the studies by Gallant (1960), Fox (1963). They compared trifluperidol at low doses versus haloperidol and chlorpromazine at medium and high doses, BPRS anergia factor improved only at low doses. Diphenylbutylpiperidines (DPBP): Meltzer's review (1986) concluded to the efficacy of such drugs on negative symptoms appearing as a specific biochemical relationship effect. A definite analysis about doses leads to a very different interpretation: DPBP low doses and only low doses improved negative symptoms as much as some low doses of phenothiazines. On the opposite, DPBP, phenothiazines and butyrophenones high doses are inefficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1683624

  2. Unexpected Analyte Oxidation during Desorption Electrospray Ionization - Mass Spectrometry

    SciTech Connect

    Pasilis, Sofie P; Kertesz, Vilmos; Van Berkel, Gary J

    2008-01-01

    During the analysis of surface spotted analytes using desorption electrospray ionization mass spectrometry (DESI-MS), abundant ions are sometimes observed that appear to be the result of oxygen addition reactions. In this investigation, the effect of sample aging, the ambient lab environment, spray voltage, analyte surface concentration, and surface type on this oxidative modification of spotted analytes, exemplified by tamoxifen and reserpine, during analysis by desorption electrospray ionization mass spectrometry was studied. Simple exposure of the samples to air and to ambient lighting increased the extent of oxidation. Increased spray voltage lead also to increased analyte oxidation, possibly as a result of oxidative species formed electrochemically at the emitter electrode or in the gas - phase by discharge processes. These oxidative species are carried by the spray and impinge on and react with the sampled analyte during desorption/ionization. The relative abundance of oxidized species was more significant for analysis of deposited analyte having a relatively low surface concentration. Increasing spray solvent flow rate and addition of hydroquinone as a redox buffer to the spray solvent were found to decrease, but not entirely eliminate, analyte oxidation during analysis. The major parameters that both minimize and maximize analyte oxidation were identified and DESI-MS operational recommendations to avoid these unwanted reactions are suggested.

  3. Influence of Sterilized Human Fecal Extract on the Sensitivity of Salmonella enterica ATCC 13076 and Listeria monocytogenes ATCC 15313 to Enrofloxacin

    PubMed Central

    Ahn, Youngbeom; Stuckey, Ryan; Sung, Kidon; Rafii, Fatemeh; Cerniglia, Carl E.

    2013-01-01

    There is much debate on whether continuous exposure of commensal bacteria and potential pathogens residing in the human intestinal tract to low levels of antimicrobial agents from treated food animals pose a public health concern. To investigate antimicrobial effects on bacteria under colonic conditions, we studied resistance development in Salmonella enterica and Listeria monocytogenes exposed to enrofloxacin in the presence of fecal extract. The bacteria were incubated at 37 °C in Mueller-Hinton broth, with and without 0.01~0.5 μg/mL enrofloxacin, in the presence and absence of sucrose, and with 1% or 2.5% filter-sterilized fecal extract, for three passages. In the second and third passages, only the bacteria incubated in the media containing sterilized fecal extract grew in 0.5 μg/mL of enrofloxacin. Fecal extract (1% and 2.5%) decreased the sensitivity of S. enterica to enrofloxacin in the medium containing the efflux pump inhibitors reserpine and carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and affected the accumulation of ethidium bromide (EtBr) in this bacterium. Enrofloxacin (0.06 µg/mL) and fecal extract altered the composition of fatty acids in S. enterica and L. monocytogenes. We conclude that fecal extract decreased the susceptibilities of S. enterica and L. monocytogenes to concentrations of enrofloxacin higher than the MIC and resulted in rapid resistance selection. PMID:27029316

  4. Quantification and characterization of alkaloids from roots of Rauwolfia serpentina using ultra-high performance liquid chromatography-photo diode array-mass spectrometry.

    PubMed

    Sagi, Satyanarayanaraju; Avula, Bharathi; Wang, Yan-Hong; Khan, Ikhlas A

    2016-01-01

    A new UHPLC-UV method has been developed for the simultaneous analysis of seven alkaloids [ajmaline (1), yohimbine (2), corynanthine (3), ajmalicine (4), serpentine (5), serpentinine (6), and reserpine (7)] from the root samples of Rauwolfia serpentina (L.) Benth. ex Kurz. The chromatographic separation was achieved using a reversed phase C18 column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. The seven compounds were completely separated within 8 min at a flow rate of 0.2 mL/min with a 2-μL injection volume. The method is validated for linearity, accuracy, repeatability, limits of detection (LOD), and limits of quantification (LOQ). Seven plant samples and 21 dietary supplements claiming to contain Rauwolfia roots were analyzed and content of total alkaloids (1-7) varied, namely, 1.57-12.1 mg/g dry plant material and 0.0-4.5 mg/day, respectively. The results indicated that commercial products are of variable quality. The developed analytical method is simple, economic, fast, and suitable for quality control analysis of Rauwolfia samples and commercial products. The UHPLC-QToF-mass spectrometry with electrospray ionization (ESI) interface method is described for the confirmation and characterization of alkaloids from plant samples. This method involved the detection of [M + H](+) or M(+) ions in the positive mode. PMID:26476922

  5. Lycaenid Caterpillar Secretions Manipulate Attendant Ant Behavior.

    PubMed

    Hojo, Masaru K; Pierce, Naomi E; Tsuji, Kazuki

    2015-08-31

    Mutualistic interactions typically involve the exchange of different commodities between species. Nutritious secretions are produced by a number of insects and plants in exchange for services such as defense. These rewards are valuable metabolically and can be used to reinforce the behavior of symbiotic partners that can learn and remember them effectively. We show here novel effects of insect exocrine secretions produced by caterpillars in modulating the behavior of attendant ants in the food-for-defense interaction between lycaenid butterflies and ants. Reward secretions from the dorsal nectary organ (DNO) of Narathura japonica caterpillars function to reduce the locomotory activities of their attendant ants, Pristomyrmex punctatus workers. Moreover, workers that feed from caterpillar secretions are significantly more likely to show aggressive responses to eversion of the tentacle organs of the caterpillars. Analysis of the neurogenic amines in the brains of workers that consumed caterpillar secretions showed a significant decrease in levels of dopamine compared with controls. Experimental treatments in which reserpine, a known inhibitor of dopamine in Drosophila, was fed to workers similarly reduced their locomotory activity. We conclude that DNO secretions of lycaenid caterpillars can manipulate attendant ant behavior by altering dopaminergic regulation and increasing partner fidelity. Unless manipulated ants also receive a net nutritional benefit from DNO secretions, this suggests that similar reward-for-defense interactions that have been traditionally considered to be mutualisms may in fact be parasitic in nature. PMID:26234210

  6. Chemical enhancement of SA7 virus transformation of hamster embryo cells: evaluation by interlaboratory testing of diverse chemicals.

    PubMed

    Hatch, G G; Anderson, T M; Lubet, R A; Kouri, R E; Putman, D L; Cameron, J W; Nims, R W; Most, B; Spalding, J W; Tennant, R W

    1986-01-01

    Twelve chemicals from diverse structural classes were tested under code for their capacity to enhance the transformation of Syrian hamster embryo cells by simian adenovirus SA7 in two independent laboratories. Pretreatment of hamster cells with eight of those chemicals (reserpine, dichlorvos, methapyrilene hydrochloride, benzidine dihydrochloride, diphenylhydantoin, cinnamyl anthranilate, 11-aminoundecanoic acid, and 4,4'-oxydianiline) produced repeatable enhancement of SA7 transformation at two or more consecutive dose levels, which constitutes clear evidence of enhancing activity in this assay. Both toxic and nontoxic doses of each of these chemicals caused enhancement of virus transformation. Two chemicals (2,6-dichloro-p-phenylenediamine and cinnamaldehyde) produced some evidence of enhancing activity (repeatable transformation enhancement at one dose). Dose ranges for cytotoxicity and enhancement of SA7 transformation were similar in both laboratories for all chemicals producing activity. The final two chemicals, chloramphenicol sodium succinate and ethylene thiourea, failed to reproducibly demonstrate either significant cytotoxicity or enhancement of SA7 transformation at concentrations up to 10-20 mM. The test results for these 12 chemicals were combined with the test results for 9 known carcinogens and noncarcinogens in order to evaluate relationships between activity, dose response, and lowest effective enhancing concentration for these compounds, as well as to correlate them with rodent carcinogenesis classifications. The Syrian hamster embryo cell-SA7 system demonstrated reproducible test responses in both intra- and interlaboratory studies and detected 13 out of 15 known rodent carcinogens. PMID:3732194

  7. Determination of loperamide in mdr1a/1b knock-out mouse brain tissue using matrix-assisted laser desorption/ionization mass spectrometry and comparison with quantitative electrospray-triple quadrupole mass spectrometry analysis.

    PubMed

    Shin, Young G; Dong, Teresa; Chou, Bilin; Menghrajani, Kapil

    2011-11-01

    Recently matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) imaging has been used to analyze small molecule pharmaceutical compounds directly on tissue sections to determine spatial distribution within target tissue and organs. The data presented to date usually indicate relative amounts of drug within the tissue. The determination of absolute amounts is still done using tissue homogenization followed by traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, the quantitative determination of loperamide, an antidiarrheal agent and a P-glycoprotein substrate, in mdr1a/1b (-/-) mouse brain tissue sections using MALDI MS on a quadrupole time-of-flight mass spectrometry is described. 5 mg/mL α-cyano-4-hydroxycinnamic acid in 50% acetonitrile with 0.1% trifluoroacetic acid and 0.5 μM reserpine was used as the MALDI matrix. The calibration curve constructed by the peak intensities of standard samples from MALDI MS was linear from 0.025 to 0.5 μM with r² = 0.9989. The accuracy of calibration curve standards was 78.3-105.9% and the percent deviation was less than 25%. Comparison between direct MALDI tissue analysis and conventional tissue analysis using homogenization followed by electrospray LC-MS/MS was also explored. PMID:22139698

  8. Bystander effects of ionizing radiation can be modulated by signaling amines

    SciTech Connect

    Poon, R.C.C.; Agnihotri, N.; Seymour, C.; Mothersill, C.

    2007-10-15

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca{sup 2+} ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects.

  9. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    PubMed

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  10. Elucidation of the Intestinal Absorption Mechanism of Celastrol Using the Caco-2 Cell Transwell Model.

    PubMed

    Li, Hong; Li, Jie; Liu, Lu; Zhang, Yichuan; Luo, Yili; Zhang, Xiaoli; Yang, Peng; Zhang, Manna; Yu, Weifeng; Qu, Shen

    2016-08-01

    Celastrol, a triterpenoid isolated from stem (caulis) of Celastrus orbiculatus Thunb. (Celastraceae), has been known to have various pharmacological effects, including anti-inflammatory, anticancer, and antioxidant activities. However, the mechanism of the intestinal absorption of celastrol is unknown. The aim of this study was to investigate the intestinal absorption of celastrol using the Caco-2 cell transwell model. First, the bidirectional transport of celastrol in Caco-2 cell monolayers was observed. Then, the effects of time, concentration, temperature, paracellular pathway, and efflux transport inhibition on the transport of celastrol across the Caco-2 cell monolayers were investigated. The P-glycoprotein inhibitor verapamil and cyclosporin A, the multidrug resistance protein 2 inhibitor MK571, and the breast cancer resistance protein inhibitor reserpine were used. Additionally, the effects of celastrol on the activity of P-glycoprotein were evaluated using the rhodamine 123 uptake assay. In this study, we found that the intestinal transport of celastrol was a time- and concentration-dependent active transport. The paracellular pathway was not involved in the transport of celastrol, and the efflux of celastrol was energy dependent. The results indicated that celastrol is a substrate of P-glycoprotein but not multidrug resistance protein 2 or the breast cancer resistance protein. In addition, celastrol could not affect the uptake of rhodamine 123 in Caco-2 cells, which indicated that celastrol could not inhibit or induce the activity of P-glycoprotein. PMID:27159672

  11. Electrochemical Imaging of Dopamine Release from Three-Dimensional-Cultured PC12 Cells Using Large-Scale Integration-Based Amperometric Sensors.

    PubMed

    Abe, Hiroya; Ino, Kosuke; Li, Chen-Zhong; Kanno, Yusuke; Inoue, Kumi Y; Suda, Atsushi; Kunikata, Ryota; Matsudaira, Masahki; Takahashi, Yasufumi; Shiku, Hitoshi; Matsue, Tomokazu

    2015-06-16

    In the present study, we used a large-scale integration (LSI)-based amperometric sensor array system, designated Bio-LSI, to image dopamine release from three-dimensional (3D)-cultured PC12 cells (PC12 spheroids). The Bio-LSI device consists of 400 sensor electrodes with a pitch of 250 μm for rapid electrochemical imaging of large areas. PC12 spheroids were stimulated with K(+) to release dopamine. Poststimulation dopamine release from the PC12 spheroids was electrochemically imaged using the Bio-LSI device. Bio-LSI clearly showed the effects of the dopaminergic drugs l-3,4-dihydroxyphenylalanine (L-DOPA) and reserpine on K(+)-stimulated dopamine release from PC12 spheroids. Our results demonstrate that dopamine release from PC12 spheroids can be monitored using the device, suggesting that the Bio-LSI is a promising tool for use in evaluating 3D-cultured dopaminergic cells and the effects of dopaminergic drugs. To the best of our knowledge, this report is the first to describe electrochemical imaging of dopamine release by PC12 spheroids using LSI-based amperometric sensors. PMID:25971414

  12. Traditional knowledge and formulations of medicinal plants used by the traditional medical practitioners of bangladesh to treat schizophrenia like psychosis.

    PubMed

    Ahmed, Md Nasir; Kabidul Azam, Md Nur

    2014-01-01

    Schizophrenia is a subtle disorder of brain development and plasticity; it affects the most basic human processes of perception, emotion, and judgment. In Bangladesh the traditional medical practitioners of rural and remote areas characterized the schizophrenia as an insanity or a mental problem due to possession by ghosts or evil spirits and they have used various plant species' to treat such symptoms. The aim of the present study was to conduct an ethnomedicinal plant survey and documentation of the formulations of different plant parts used by the traditional medical practitioners of Rangamati district of Bangladesh for the treatment of schizophrenia like psychosis. It was observed that the traditional medical practitioners used a total of 15 plant species to make 14 formulations. The plants were divided into 13 families, used for treatment of schizophrenia and accompanying symptoms like hallucination, depression, oversleeping or insomnia, deterioration of personal hygiene, forgetfulness, and fear due to evil spirits like genies or ghost. A search of the relevant scientific literatures showed that a number of plants used by the medicinal practitioners have been scientifically validated in their uses and traditional medicinal knowledge has been a means towards the discovery of many modern medicines. Moreover, the antipsychotic drug reserpine, isolated from the dried root of Rauvolfia serpentina species, revolutionized the treatment of schizophrenia. So it is very much possible that formulations of the practitioner, when examined scientifically in their entireties, can form discovery of lead compounds which can be used as safe and effective antipsychotic drug to treat schizophrenia. PMID:25101175

  13. The Behavioral Actions of Lithium in Rodent Models

    PubMed Central

    O’Donnell, Kelley C.; Gould, Todd D.

    2007-01-01

    For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium. PMID:17532044

  14. Expediting the method development and quality control of reversed-phase liquid chromatography electrospray ionization mass spectrometry for pharmaceutical analysis by using an LC/MS performance test mix.

    PubMed

    Tang, L; Fitch, W L; Alexander, M S; Dolan, J W

    2000-11-01

    Mass spectrometry combined with liquid chromatography (LC/MS) has become an important analytical methodology in both pharmaceutical and biomolecule analyses. LC/MS, especially with reversed-phase HPLC (RP-LC), is extensively used in the separation and structural identification of pharmaceutical samples. However, many parameters have to be considered when a new LC/MS method is developed for either separation and structural analysis of unknown mixtures or quantitative analysis of a set of known compounds in an assay. The optimization of a new LC/MS method can be a time-consuming process. A novel kit-LC/MS performance test mix-composed of aspartame, cortisone, reserpine, and dioctyl phthalate has been developed to accelerate the process of establishing a new RP-LC/MS method. The LC/MS mix makes the evaluation and validation of an LC/MS method more efficient and easier. It also simplifies the quality control procedure for an LC/MS method in use. PMID:11080866

  15. Development of (S)-N6-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: Potent in vivo activity in Parkinson’s disease animal models

    PubMed Central

    Ghosh, Balaram; Antonio, Tamara; Zhen, Juan; Kharkar, Prashant; Reith, Maarten E. A.; Dutta, Aloke K.

    2010-01-01

    Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (Ki). Functional activity of selected compounds in stimulating GTPγS binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. SAR results identified compound (−)-24c (D-301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTPγS); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (−)-24b and (−)-24c exhibited potent radical scavenging activity. The two lead compounds (−)-24b and (−)-24c exhibited high in vivo activity in two Parkinson’s disease (PD) animal models, reserpinized rat model and 6-OH-DA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD. PMID:20038106

  16. Ethidium Bromide MIC Screening for Enhanced Efflux Pump Gene Expression or Efflux Activity in Staphylococcus aureus▿

    PubMed Central

    Patel, Diixa; Kosmidis, Christos; Seo, Susan M.; Kaatz, Glenn W.

    2010-01-01

    Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in Staphylococcus aureus. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed. Ethidium bromide is a substrate for all but one of the characterized S. aureus multidrug-resistant (MDR) efflux pumps (NorC), leading us to examine the utility of simple broth microtiter MIC determinations using this compound in identifying efflux-proficient strains. Quantitative reverse transcription-PCR identified the increased expression of one or more MDR efflux pump genes in 151/309 clinical strains (49%). Ethidium bromide MIC testing was insensitive (48%) but specific (92%) in identifying strains with gene overexpression, but it was highly sensitive (95%) and specific (99%) in identifying strains capable of ethidium efflux. The increased expression of norA with or without other genes was most commonly associated with efflux, and in the majority of cases that efflux was inhibited by reserpine. Ethidium bromide MIC testing is a simple and straightforward method to identify effluxing strains and can provide accurate predictions of efflux prevalence in large strain sets in a short period of time. PMID:20855743

  17. Traditional Knowledge and Formulations of Medicinal Plants Used by the Traditional Medical Practitioners of Bangladesh to Treat Schizophrenia Like Psychosis

    PubMed Central

    Kabidul Azam, Md. Nur

    2014-01-01

    Schizophrenia is a subtle disorder of brain development and plasticity; it affects the most basic human processes of perception, emotion, and judgment. In Bangladesh the traditional medical practitioners of rural and remote areas characterized the schizophrenia as an insanity or a mental problem due to possession by ghosts or evil spirits and they have used various plant species' to treat such symptoms. The aim of the present study was to conduct an ethnomedicinal plant survey and documentation of the formulations of different plant parts used by the traditional medical practitioners of Rangamati district of Bangladesh for the treatment of schizophrenia like psychosis. It was observed that the traditional medical practitioners used a total of 15 plant species to make 14 formulations. The plants were divided into 13 families, used for treatment of schizophrenia and accompanying symptoms like hallucination, depression, oversleeping or insomnia, deterioration of personal hygiene, forgetfulness, and fear due to evil spirits like genies or ghost. A search of the relevant scientific literatures showed that a number of plants used by the medicinal practitioners have been scientifically validated in their uses and traditional medicinal knowledge has been a means towards the discovery of many modern medicines. Moreover, the antipsychotic drug reserpine, isolated from the dried root of Rauvolfia serpentina species, revolutionized the treatment of schizophrenia. So it is very much possible that formulations of the practitioner, when examined scientifically in their entireties, can form discovery of lead compounds which can be used as safe and effective antipsychotic drug to treat schizophrenia. PMID:25101175

  18. Natural products as potential human ether-a-go-go-related gene channel inhibitors - screening of plant-derived alkaloids.

    PubMed

    Schramm, Anja; Saxena, Priyanka; Chlebek, Jakub; Cahlíková, Lucie; Baburin, Igor; Hering, Steffen; Hamburger, Matthias

    2014-06-01

    Inhibition of the cardiac human ether-a-go-go-related gene channel is a problematic off-target pharmacological activity and, hence, a major safety liability in clinical practice. Several non-cardiac drugs have been restricted in their use, or even removed from the market due to this potentially fatal adverse effect. Comparatively little is known about the human ether-a-go-go-related gene inhibitory potential of plant-derived compounds. In the course of an ongoing human ether-a-go-go-related gene in vitro study, a total of 32 structurally diverse alkaloids of plant origin as well as two semi-synthetically obtained protoberberine derivatives were screened by means of an automated Xenopus oocyte assay. Protopine, (+)-bulbocapnine, (+)-N-methyllaurotetanine, (+)-boldine, (+)-chelidonine, (+)-corynoline, reserpine, and yohimbine reduced the human ether-a-go-go-related gene current by ≥ 50% at 100 µM, and were submitted to concentration-response experiments. Our data show that some widely occurring plant-derived alkaloids carry a potential risk for human ether-a-go-go-related gene toxicity. PMID:24963621

  19. Extrapyramidal system neurotoxicity: animal models.

    PubMed

    Dorman, David

    2015-01-01

    The central nervous system's extrapyramidal system provides involuntary motor control to the muscles of the head, neck, and limbs. Toxicants that affect the extrapyramidal system are generally clinically characterized by impaired motor control, which is usually the result of basal ganglionic dysfunction. A variety of extrapyramidal syndromes are recognized in humans and include Parkinson's disease, secondary parkinsonism, other degenerative diseases of the basal ganglia, and clinical syndromes that result in dystonia, dyskinesia, essential tremor, and other forms of tremor and chorea. This chapter briefly reviews the anatomy of the extrapyramidal system and discusses several naturally occurring and experimental models that target the mammalian (nonhuman) extrapyramidal system. Topics discussed include extrapyramidal syndromes associated with antipsychotic drugs, carbon monoxide, reserpine, cyanide, rotenone, paraquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and manganese. In most cases, animals are used as experimental models to improve our understanding of the toxicity and pathogenesis of these agents. Another agent discussed in this chapter, yellowstar thistle poisoning in horses, however, represents an important spontaneous cause of parkinsonism that naturally occurs in animals. The central focus of the chapter is on animal models, especially the concordance between clinical signs, neurochemical changes, and neuropathology between animals and people. PMID:26563791

  20. Direct effect of cadmium on blood pressure and adrenergic system in the cat

    SciTech Connect

    Revis, N.W.; Bingham, G.

    1984-01-01

    The dose-response effect of cadmium on systolic and diastolic pressure were measured in the cat after injecting a bolus of cadmium intravenously. In animals treated with 100, 125, or 150 ug cadmium/kg BW systolic and diastolic pressure were both significantly increased. These increases were gradual as the dose Cd was increased from 75 to 125 ug. In an attempt to determine the mechanism associated with cadmium-induced hypertension in the cat the effect of this element on the adrenergic system was studied. The effect of ..cap alpha.. and BETA agonists on cadmium-induced increase in blood pressure were determined by the injection of either propranolol or phentolamine at 20 mg/kg BW. The hypertensive effect of 125 ug Cd was abolished by phentolamine but not by propranolol suggesting, that Cd may induce the release of norepinephrine from storage sites. In support of this suggestion we observed in cats treated with 125 ug Cd a significant increase in plasma norepinephrine which was not affected by propranolol or phentolamine injections. However reserpine pretreatment abolished both the increase in plasma norepinephrine and the cadmium-induced hypertensive effect. The data suggest that the associated mechanism of cadmium-induced hypertension may be related to the effect of this element of the release of norepinephrine. Increases in the extracellular levels of this neurotransmitter in turn provokes a rise in blood pressure through its interaction with the receptors of vascular smooth muscle cells. 38 references, 7 figures, 1 table.

  1. Reversal by pronethalol of dibenamine blockade

    PubMed Central

    Guimarães, S.

    1969-01-01

    1. The guinea-pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving α-adrenoceptive receptors, because no β-receptors were found in this preparation. 2. Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7·1 × 10-6M, 1·5 × 10-5M and 2·7 × 10-5M, respectively. 3. Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine. 4. Pronethalol (6·8 × 10-5M) reversed the α-receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine. 5. Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose-effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol. 6. It is assumed that the reversal is dependent on a direct action on α-receptors, “spare receptors” being probably involved. PMID:4389284

  2. Catecholamines up Integrates Dopamine Synthesis and Synaptic Trafficking

    PubMed Central

    Wang, Zhe; Ferdousy, Faiza; Lawal, Hakeem; Huang, Zhinong; Daigle, J. Gavin; Izevbaye, Iyare; Doherty, Olugbenga; Thomas, Jerrad; Stathakis, Dean G; O’Donnell, Janis M.

    2011-01-01

    The highly reactive nature of dopamine renders dopaminergic neurons vulnerable to oxidative damage. We recently demonstrated that loss-of-function mutations in the Drosophila gene Catecholamines up (Catsup) elevate dopamine pools but, paradoxically, also confer resistance to paraquat, an herbicide that induces oxidative stress-mediated toxicity in dopaminergic neurons. We now report a novel association of the membrane protein, Catsup, with GTP cyclohydrolase rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis and tyrosine hydroxylase, rate-limiting enzyme for dopamine biosynthesis, which requires BH4 as a cofactor. Loss-of-function Catsup mutations cause dominant hyperactivation of both enzymes. Elevated dopamine levels in Catsup mutants coincide with several distinct characteristics, including hypermobility, minimal basal levels of 3,4-Dihydroxy-Phenylacetic Acid, an oxidative metabolite of dopamine, and resistance to the Vesicular Monoamine Transporter inhibitor, reserpine, suggesting that excess dopamine is synaptically active and that Catsup functions in the regulation of synaptic vesicle loading and release of dopamine. We conclude that Catsup regulates and links the dopamine synthesis and transport networks. PMID:21985068

  3. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog

    SciTech Connect

    Akiyama, S.; Cornwell, M.M.; Kuwano, M.; Pastan, I.; Gottesman, M.M.

    1988-02-01

    Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.

  4. Behavioral effects of β-phenylethylamine and various monomethylated and monohalogenated analogs in mice are mediated by catecholaminergic mechanisms.

    PubMed

    Mosnaim, Aron D; Hudzik, Thomas; Wolf, Marion E

    2015-01-01

    The effects of the administration [intraperitoneally, 15 and 75 mg/kg, except α-MePEA (amphetamine, AMPH) at 5 and 10 mg/kg] of β-phenylethylamine (PEA), its methylated (o-Me-, p-Me-, α-Me-, β-Me-, N-Me-, p-OMe-, N,N-di-Me-, and 3,4-diOH-N-Me-), para-halogenated (Br-, Cl-, F-, and I-), and other derivatives for example, p-OHPEA (p-tyramine), on Swiss male albino mice caged behavior fall into 3 broad categories. (1) N,N-diMe-, 3,4-diOH-N-Me-, and o-MePEA tend to reduce the behavioral activity, (2) p-OH and p-IPEA were without noticeable effects, and (3) the remaining compounds increased locomotor activity, produced hyperexcitability and fighting, jumping and vocalization, and convulsion in a graded manner (listed in increasing order p-OMe-, β-Me-, p-Cl-, p-Br-, p-F-, p-Me-, and N-MePEA, PEA itself and α-MePEA). The latter compound (amphetamine) being the most potent among them; equieffective but with lower potency were p-MePEA, N-MePEA, and PEA itself. The effects of PEAs upon group cage behavior were increased by pretreatment with pargyline (1.5 hours; 15 mg/kg) and decreased after reserpine or haloperidol [4 hours and/or 24 hours (2.5 and/or 2.5 mg/kg) and 1 hour (1 mg/kg), respectively], reaching full suppression with the double-dose regimen of reserpine and single dose of haloperidol. As expected, none of these substances by themselves were noticeable changed group mice activity or stereotypic behavior. The effects of test amines and catecholamine-modulating agents on stereotypy were assessed by rating the sequentially occurring behaviors: increased exploratory behavior with increased sniffing; occasional side-to-side head weaving; paw-licking and other grooming; gnawing, fighting and continuous side-to-side head weaving, and periodic episodes of "popcorn" behavior, during which all mice in the cage ran, jumped, and vocalized. In general, rank efficacy in eliciting stereotype aligned with rank efficacy in affecting group cage behavior. Our results show

  5. Monoamines and their metabolites in the avian brain.

    PubMed

    Juorio, A V; Vogt, M

    1967-04-01

    1. In the avian brain, a high concentration of dopamine was found in a sharply contoured region of the nucleus basalis which may or may not have included the nucleus entopeduncularis, and therefore lay within the palaeostriatum of the nomenclature of Crosby and Huber. This was thus the only region which may be considered biochemically homologous to the mammalian corpus striatum. For purposes of macroscopic identification only, the region is described here as the ;anterior part of the nucleus basalis'. The concentration of dopamine was 3 mug/g in the pigeon, about the same in the duck and chicken, and 7.5 mug/g in the finch. In the pigeon this region also contained some noradrenaline; the quantity of 5-hydroxytryptamine (1.4 mug/g) and 5-hydroxyindolylacetic acid (0.6 mug/g) was larger than in any other part of the brain.2. In the brain of the pigeon and the chicken, the highest concentrations of noradrenaline (1.5 and 1.4 mug/g) were found in the hypothalamus.3. The concentration of adrenaline was higher in the avian than in the mammalian brain. In the hypothalamus, it ranged from 0.4 mug/g in the pigeon to 1 mug/g in the chicken.4. Fluorescence microscopy, using the formaldehyde condensation method, showed, in the anterior part of the nucleus basalis, a large area of diffuse green-yellow fluorescence, similar in appearance to the fluorescence of the striatum of the rat. In addition this part of the brain contained a small region of fluorescent fibres and varicosities. It is suggested that the diffuse fluorescence was produced by dopamine. It was absent from brains of reserpine-treated pigeons.5. In the pigeon, reserpine, tetrabenazine and prenylamine produced a decrease in the concentration of brain monoamines, an effect which was comparable to that seen in mammals. Yet, none of these drugs raised the concentration of homovanillic acid, but they increased that of 5-hydroxyindolylacetic acid; these drugs raise the concentration of both acids in mammalian brain.6

  6. An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice

    PubMed Central

    Das, Abhishek; Panja, Sourav; Mandal, Nripendranath

    2015-01-01

    Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls’ staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for

  7. Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species.

    PubMed

    Góngora-Castillo, Elsa; Childs, Kevin L; Fedewa, Greg; Hamilton, John P; Liscombe, David K; Magallanes-Lundback, Maria; Mandadi, Kranthi K; Nims, Ezekiel; Runguphan, Weerawat; Vaillancourt, Brieanne; Varbanova-Herde, Marina; Dellapenna, Dean; McKnight, Thomas D; O'Connor, Sarah; Buell, C Robin

    2012-01-01

    The natural diversity of plant metabolism has long been a source for human medicines. One group of plant-derived compounds, the monoterpene indole alkaloids (MIAs), includes well-documented therapeutic agents used in the treatment of cancer (vinblastine, vincristine, camptothecin), hypertension (reserpine, ajmalicine), malaria (quinine), and as analgesics (7-hydroxymitragynine). Our understanding of the biochemical pathways that synthesize these commercially relevant compounds is incomplete due in part to a lack of molecular, genetic, and genomic resources for the identification of the genes involved in these specialized metabolic pathways. To address these limitations, we generated large-scale transcriptome sequence and expression profiles for three species of Asterids that produce medicinally important MIAs: Camptotheca acuminata, Catharanthus roseus, and Rauvolfia serpentina. Using next generation sequencing technology, we sampled the transcriptomes of these species across a diverse set of developmental tissues, and in the case of C. roseus, in cultured cells and roots following elicitor treatment. Through an iterative assembly process, we generated robust transcriptome assemblies for all three species with a substantial number of the assembled transcripts being full or near-full length. The majority of transcripts had a related sequence in either UniRef100, the Arabidopsis thaliana predicted proteome, or the Pfam protein domain database; however, we also identified transcripts that lacked similarity with entries in either database and thereby lack a known function. Representation of known genes within the MIA biosynthetic pathway was robust. As a diverse set of tissues and treatments were surveyed, expression abundances of transcripts in the three species could be estimated to reveal transcripts associated with development and response to elicitor treatment. Together, these transcriptomes and expression abundance matrices provide a rich resource for

  8. Cannabinoid agonists stimulate [3H]GABA release in the globus pallidus of the rat when G(i) protein-receptor coupling is restricted: role of dopamine D2 receptors.

    PubMed

    Gonzalez, Brenda; Paz, Francisco; Florán, Leonor; Aceves, Jorge; Erlij, David; Florán, Benjamín

    2009-03-01

    The motor effects of cannabinoids in the globus pallidus appear to be caused by increases in interstitial GABA. To elucidate the mechanism of this response, we investigated the effect of the selective cannabinoid type 1 receptor (CB1) cannabinoid agonist arachidonyl-2-chloroethylamide (ACEA) on [(3)H]GABA release in slices of the rat globus pallidus. ACEA had two effects: concentrations between 10(-8) and 10(-6) M stimulated release, whereas higher concentrations (IC(50) approximately 10(-6) M) inhibited it. Another cannabinoid agonist, WIN-55,212-2, also had bimodal effects on release. Studies of cAMP production indicate that under conditions of low G(i/o), availability the coupling of CB1 receptors with G(i/o) proteins can be changed into CB1:G(s/olf) coupling; therefore, we determined the effects of conditions that limit G(i/o) availability on [(3)H]GABA release. Blockers of G(i/o) protein interactions, pertussis toxin and N-ethylmaleimide, transformed the inhibitory effects of ACEA on GABA release into stimulation. It also has been suggested that stimulation of D2 receptors can reduce G(i/o) availability. Blocking D2 receptors with sulpiride [(S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxybenzamidersqb] or depleting dopamine with reserpine inhibited the ACEA-induced stimulation of release. Thus, the D2 dependence of stimulation is consistent with the proposal that D2 receptors reduce G(i/o) proteins available for binding to the CB1 receptor. In summary, CB1 receptor activation has dual effects on GABA release in the globus pallidus. Low concentrations stimulate release through a process that depends on activation of dopamine D2 receptors that may limit G(i/o) protein availability. Higher concentrations of cannabinoid inhibit GABA release through mechanisms that are independent of D2 receptor activation. PMID:19106171

  9. Screening approach by ultra-high performance liquid chromatography-tandem mass spectrometry for the blood quantification of thirty-four toxic principles of plant origin. Application to forensic toxicology.

    PubMed

    Carlier, Jérémy; Guitton, Jérôme; Romeuf, Ludovic; Bévalot, Fabien; Boyer, Baptiste; Fanton, Laurent; Gaillard, Yvan

    2015-01-15

    Plant poisonings have left their mark on history and still cause many deaths, whether intentional or accidental. The means to show toxicological evidence of such poisonings should be implemented with great care. This article presents a technique for measuring thirty-nine toxic principles of plant origin in the blood, covering a large amount of toxins from local or exotic plants: α-lobeline, α-solanine, aconitine, ajmaline, atropine, brucine, cephalomannine, colchicine, convallatoxin, cymarine, cytisine, digitoxin, digoxin, emetine, gelsemine, ibogaine, jervine, kavain, lanatoside C, lupanine, mitragynine, neriifolin, oleandrin, ouabain, paclitaxel, physostigmine, pilocarpine, podophyllotoxin, proscillaridin A, reserpine, retrorsine, ricinine, scopolamine, senecionine, sparteine, strophanthidin, strychnine, veratridine and yohimbine. Analysis was carried out using an original ultra-high performance liquid chromatography separation coupled with tandem mass spectrometry detection. Extraction was a standard solid phase extraction performed on Oasis(®) HLB cartridge. Thirty-four of the thirty-nine compounds were put through a validation procedure. The assay was linear in the calibration curve range from 0.5 or 5 μg/L to 1000 μg/L according to the compounds. The method is sensitive (LOD from 0.1 to 1.6 μg/L). The within-day precision of the assay was less than 22.5% at the LLOQ, and the between-day precision was less than 21.5% for 10 μg/L for all the compounds included. The assay accuracy was in the range of 87.4 to 119.8% for the LLOQ. The extraction recovery and matrix effect ranged from 30 to 106% and from -30 to 14%, respectively. It has proven useful and effective in several difficult forensic cases. PMID:25438245

  10. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    PubMed

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968

  11. Some neurochemical effects of amphetamine, methylamphetamine and p-bromomethyl-amphetamine in the rat

    PubMed Central

    Leonard, B. E.; Shallice, Susan A.

    1971-01-01

    1. Low doses of D-amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p-Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; D-amphetamine produced the greatest and p-bromomethylamphetamine the least increase in motor activity. 2. D-Amphetamine and D-methylamphetamine potentiated the action of 4,α-dimethyl-m-tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by D-amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism. 3. Differences were found in the effect of the three drugs on brain dopamine concentrations; D-amphetamine caused a decrease while p-bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p-bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77. 4. Methylamphetamine and p-bromomethylamphetamine reduced the concentration of 5-hydroxytryptamine (5-HT) in the brain; administration of the same dose of D-amphetamine did not change the concentration of 5-HT. 5. Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ-amino-n-butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain. PMID:5572273

  12. Presence of neuropeptide Y in the rat seminal vesicle and its effects on noradrenaline- and nerve-induced contractions.

    PubMed Central

    Iravani, M M; Zar, M A

    1994-01-01

    1. Immunohistochemical and functional studies have been performed to localize and determine the effects of neuropeptide Y (NPY) in the rat seminal vesicle. 2. An abundant presence of NPY-immunoreactive nerves, mainly concentrated in the smooth muscle layer of the seminal vesicle was found. Chronic 6-hydroxydopamine treatment (four doses of 50 mg kg-1 i.p. on days 1, 2, 4 and 6; rats killed one week after the last injection) led to a large reduction but not abolition of the NPY-immunoreactivity. 3. NPY (1-250 nM) did not affect the resting tone of the seminal vesicle. 4. The seminal vesicle was contracted by electrical field stimulation (EFS) and by exposure to 5 microM noradrenaline (NA). These contractions were abolished by phentolamine (1 microM). Tetrodotoxin (0.5 microM) abolished EFS-evoked contractions but did not affect NA-evoked contractions. 5. Seminal vesicles, from animals chronically-treated with reserpine (5 mg kg-1 i.p. on days 1 and 2; rats killed on day 3), were contracted by NA but not by EFS. 6. NPY (0.25-250 nM), concentration-dependently, inhibited EFS-evoked contractions by up to 70% maximum inhibition. Contractions evoked by EFS with short trains of pulses were inhibited by NPY to a greater degree than those with longer trains. 7. NPY had no significant effect on NA-evoked contractions. 8. These data provide strong evidence that the motor transmission in rat seminal vesicle is predominantly if not exclusively, adrenergic. It is further concluded that a rich NPY-containing innervation is present in the smooth muscle layer of rat seminal vesicle.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:7858880

  13. Increased activity of tyrosine hydroxylase in the cerebellum of the x-irradiated dystonic rat

    SciTech Connect

    Dopico, A.M.; Rios, H.; Mayo, J.; Zieher, L.M. )

    1990-08-01

    The exposure of the cephalic end of rats to repeated doses of x-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 {plus minus} 4 ng/CE and 2.8 {plus minus} 1.5 ng/CE, respectively) and x-irradiated rats (17.1 {plus minus} 1 ng/CE and 8.3 {plus minus} 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally x-irradiated animals when compared to age-matched controls (16.4 {plus minus} 1.4 vs 6.32 {plus minus} 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 {plus minus} 23.8 vs 408.2 {plus minus} 21.5 nmol CO2/h/CE, p less than 0.01 (controls and x-treated, respectively). These results suggest that x-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

  14. Animal models of depression: are there any?

    PubMed

    O'Neil, Michael F; Moore, Nicholas A

    2003-06-01

    Simple tests for antidepressant-like activity, such as 5-HTP-induced syndrome or reserpine-induced hypomotility, are often mechanism-based tests, pharmacologically specific for certain known classes of therapeutically successful antidepressant agents. Many of these behavioural assays have been superseded by neurochemical techniques such as in vivo microdialysis. In contrast to these mechanistic-based models, investigators have also endeavoured to reproduce in the laboratory, factors that are believed to precipitate depression in people. It is a strong assumption in this approach that depression is a response to stress. This strategy profiles the consequences of chronic stress particularly psychosocial stress or early life events, in order to reproduce in animals the behavioural signs and pathologies associated with depression. The advances in the social psychological, clinical pathological and new areas such as neuroimaging research offer the possibility of establishing more sophisticated models for depression in animals with a broader range of biomarkers from the immunological and endocrinological to neurochemical and behavioural. Combining these novel insights with more traditional tests of depression may not only increase our understanding of the neurobiology of depression but also afford more precise and predictive preclinical models of depression. The responsiveness of different strains or genetically modified animals to stress is likely to be a key area of study. Furthermore we must look to individual differences in subjects, even within the same strain, to more fully understand why some individuals show pathological responses to stress whereas others appear unaffected. Conversely in validating our models using currently available treatments we must include the concept of non-responders so as not to disregard models that may extend therapeutic possibilities in these patients. PMID:12766928

  15. Changes in spectral reflexions from the iridophores of the neon tetra.

    PubMed Central

    Lythgoe, J N; Shand, J

    1982-01-01

    1. The iridescent stripe of the freshwater teleost, the neon tetra, changes from green in the daytime to violet-blue at night. 2. Spectral reflectance measurements were used to follow these colour changes. 3. Light causes a shift in reflectance to longer wavelengths in living fish and in isolated tissue from the lateral stripe. The change is reversed in darkness. 4. The spectral reflectance shifts to longer wavelengths when the fish is disturbed in darkness. No such colour changes were seen in fishes kept alive in 10(-4) M-reserpine. 5. Hypotonic Ringer solution causes a reflectance shift to longer wavelengths and hypertonic solution causes a shift to shorter wavelengths. 6. The iridescent reflexions from the lateral stripe which is continued across the iris originate from iridophores in the dermis. These iridophores contain regular stacks of broad, double-sided hexagonal plates that are about 10 nm thick. Each plate is contained within a pouch in the cytoplasm and is separated from its neighbour by approximately one quarter the wavelength of light. 7. A distinction is drawn between the physiologically active iridophores in the lateral stripe and iris that have broad hexagonal crystal plates which are very thin and the physiologically inactive iridophores that are also found in the iris, but in addition are found on the flanks below the lateral stripe, and on the head. These iridophores contain hexagonal crystals that are usually narrower than the active type, but are about 60-100 nm thick. Images Plate 1 Plate 2 Plate 3 Plate 4 Plate 5 PMID:7108777

  16. Array of Chemically Etched Fused Silica Emitters for Improving the Sensitivity and Quantitation of Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Kelly, Ryan T.; Page, Jason S.; Tang, Keqi; Smith, Richard D.

    2007-06-01

    An array of emitters has been developed for increasing the sensitivity of electrospray ionization mass spectrometry (ESI-MS). The linear array consists of 19 chemically etched fused silica capillaries arranged with 500 µm (center-to-center) spacing. The multi-emitter device has a low dead volume to facilitate coupling to capillary liquid chromatography (LC) separations. The high aspect ratio of the emitters enables operation at flow rates as low as 20 nL/min/emitter, effectively extending the benefits of nanoelectrospray to higher flow rate analyses. To accommodate the larger ion current produced by the emitter array, a multi-capillary inlet to the mass spectrometer was also constructed. The inlet, which matched the dimensions of the emitter array, effectively preserved ion transmission efficiency. Standard reserpine solutions of varying concentration were electrosprayed at 1 µL/min using the multi-emitter/multi-inlet combination, and compared to a standard, single emitter configuration. A nine-fold sensitivity enhancement was observed for the multi-emitter relative to the single emitter. A bovine serum albumin tryptic digest was also analyzed and resulted in a sensitivity increase ranging from 2.4 to 12.3-fold for the detected tryptic peptides; the varying response was attributed to reduced ion suppression under the nano-ESI conditions afforded by the emitter array. An equimolar mixture of leucine enkephalin and maltopentaose was studied to verify that ion suppression is indeed reduced for the multi-ESI array relative to a single emitter over a range of flow rates.

  17. Inhibitors of Bacterial Multidrug Efflux Pumps Potentiate Antimicrobial Photoinactivation▿

    PubMed Central

    Tegos, George P.; Masago, Kayo; Aziz, Fatima; Higginbotham, Andrew; Stermitz, Frank R.; Hamblin, Michael R.

    2008-01-01

    Antimicrobial photodynamic inactivation (APDI) combines a nontoxic photoactivatable dye or photosensitizer (PS) with harmless visible light to generate singlet oxygen and reactive oxygen species that kill microbial cells. Cationic phenothiazinium dyes, such as toluidine blue O (TBO), are the only PS used clinically for APDI, and we recently reported that this class of PS are substrates of multidrug efflux pumps in both gram-positive and gram-negative bacteria. We now report that APDI can be significantly potentiated by combining the PS with an efflux pump inhibitor (EPI). Killing of Staphylococcus aureus mediated by TBO and red light is greatly increased by coincubation with known inhibitors of the major facilitator pump (NorA): the diphenyl urea INF271, reserpine, 5′-methoxyhydnocarpin, and the polyacylated neohesperidoside, ADH7. The potentiation effect is greatest in the case of S. aureus mutants that overexpress NorA and least in NorA null cells. Addition of the EPI before TBO has a bigger effect than addition of the EPI after TBO. Cellular uptake of TBO is increased by EPI. EPI increased photodynamic inactivation killing mediated by other phenothiazinium dyes, such as methylene blue and dimethylmethylene blue, but not that mediated by nonphenothiazinium PS, such as Rose Bengal and benzoporphyrin derivative. Killing of Pseudomonas aeruginosa mediated by TBO and light was also potentiated by the resistance nodulation division pump (MexAB-OprM) inhibitor phenylalanine-arginine beta-naphthylamide but to a lesser extent than for S. aureus. These data suggest that EPI could be used in combination with phenothiazinium salts and light to enhance their antimicrobial effect against localized infections. PMID:18474586

  18. Simultaneous Determination of 10 Adulterants in Antihypertensive Functional Foods Using Multi-Walled Carbon Nanotubes-Dispersive Solid-Phase Extraction Coupled with High Performance Liquid Chromatography.

    PubMed

    Zeng, Li; Li, Yongxin; Wu, Xin; Zhang, Jing; Xie, Juan; Sun, Chengjun

    2015-10-01

    Consumption of functional foods based on extracts from selected herbs to alleviate hypertension is an increasingly common practice in China. Adulteration of these foods with pharmaceuticals can significantly impact a consumer's health. To control the quality of the functional foods effectively, a method for the simultaneous determination of 10 common adulterants including chlortalidone, hydrochlorothiazide, indapamide, metoprolol, nifedipine, nimodipine, nitrendipine, reserpine, triamterene and valsartan in antihypertensive functional foods was developed. The target chemicals in samples were ultrasonically extracted with acetonitrile, and then cleaned-up with multi-walled carbon natotubes-dispersive solid-phase extraction. Finally, the analytes were separated with a C18 column using binary mobile phases consisting of acetonitrile and 0.03 mol/L KH2PO4 solutions (pH 3.0). The flow rate of the mobile phase was 0.80 mL/min, and the column temperature was 35°C. The detection wavelength was set at 220 nm. The limits of detection and quantification of the method ranged from 0.014 to 0.053 and 0.047 to 0.178 μg/mL, respectively. The recoveries of the method were in the range of 80.1-98.1% with relative standard deviations <9.53%. The method was successfully applied to the determination of the target chemicals in real samples and simulated samples, and respirine was detected in one tonic wine sample with a concentration of 56.8 ± 1.2 mg/L. PMID:25840433

  19. Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity

    PubMed Central

    Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhnt, Donald M.

    2016-01-01

    Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure. PMID:19457119

  20. An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice.

    PubMed

    Ghate, Nikhil Baban; Chaudhuri, Dipankar; Das, Abhishek; Panja, Sourav; Mandal, Nripendranath

    2015-01-01

    Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls' staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for

  1. Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

    PubMed

    Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

    2016-09-01

    Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations. PMID:27270234

  2. Muscarinic receptor stimulation and cyclic AMP-dependent effects in guinea-pig ventricular myocardium.

    PubMed Central

    Schmied, R.; Korth, M.

    1990-01-01

    1. The effect of carbachol on force of contraction, contraction duration, intracellular Na+ activity and cyclic AMP content was studied in papillary muscles of the guinea-pig exposed to isoprenaline or the phosphodiesterase inhibitor 3-isobutyl, 1-methyl xanthine (IBMX). The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. 2. Isoprenaline (10 nM) and IBMX (100 microM) produced comparable positive inotropic effects of 9.8 and 9.7 mN, respectively. Carbachol (3 microM) attenuated the inotropic effects by 82% (isoprenaline) and by 79% (IBMX). The shortening of contraction duration which accompanied the positive inotropic effect of isoprenaline (by 14.9%) and of IBMX (by 22.4%) was not significantly affected by 3 microM carbachol. 3. The positive inotropic effect of 10 nM isoprenaline and of 100 microM IBMX was accompanied by an increase in cellular cyclic AMP content of 58 and 114%, respectively. Carbachol (3 microM) failed to reduce significantly the elevated cyclic AMP content of muscles exposed to either isoprenaline or IBMX. 4. In the quiescent papillary muscle, isoprenaline (10 nM) and IBMX (100 microM) reduced the intracellular Na+ activity by 28 and 17%, respectively. This decline was not influenced by the additional application of 3 microM carbachol. 5. The results demonstrate that muscarinic antagonism in guinea-pig ventricular myocardium exposed to cyclic AMP-elevating drugs is restricted to force of contraction. The underlying mechanism does not apparently involve the cytosolic signal molecule cyclic AMP. PMID:1691677

  3. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

    PubMed Central

    Erickson, J D; Schafer, M K; Bonner, T I; Eiden, L E; Weihe, E

    1996-01-01

    A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine-storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function. Images Fig. 3 Fig. 4 PMID:8643547

  4. Some differences in uveal reactions between cats and rabbits

    PubMed Central

    Ambache, N.; Kavanagh, L.; Whiting, Judith

    1966-01-01

    1. Miosis was observed after enucleation in unopened eyes from normal or atropinized, atropinesterase-free rabbits. Such a phenomenon was not seen in enucleated cat eyes, in which the pupils remained widely dilated, whether atropine had been administered or not. 2. Pre-treatment of the animals with reserpine did not alter this difference between the species. 3. The difference does not appear to be due to absence of irins from the cat iris, since aqueous extracts of cat irides contained a smooth-muscle-contracting activity (cat irin) extractable into ether at pH 3 and therefore consisting of lipid acid(s). 4. The difference is not due to insensitivity of the cat sphincter pupillae muscle to irins, since injections of ether-purified cat or rabbit irins into the anterior chamber of enucleated cat eyes kept at room temperature constricted the pupil; injections of histamine were ineffective. 5. In experiments on animals treated with atropine ± mepyramine I.V., photographic measurements revealed a further difference, namely in the speed of miosis after stroking the iris in vivo. The response started later in the cat, and developed more slowly, but often to a fuller extent than in the rabbit. 6. In a proportion of cat eyes there was little or no change in intraocular pressure after irritation of the iris adequate to induce maximum pupillary constriction; this was so whether mepyramine had been administered or not. 7. Possible reasons for the above species differences are discussed. ImagesFig. 1Fig. 3Fig. 5Fig. 8 PMID:4380012

  5. Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture.

    PubMed

    Yamada, Hiroshi; Hayashi, Mitsuko; Uehara, Shunsuke; Kinoshita, Mika; Muroyama, Akiko; Watanabe, Masami; Takei, Koji; Moriyama, Yoshinori

    2002-05-01

    5-hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture. Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an alpha antagonist, but not by propranolol, a beta antagonist. Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release. Agents that trigger L-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis. These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles. PMID:12065661

  6. Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart.

    PubMed

    Abete, P; Testa, G; Galizia, G; Mazzella, F; Della Morte, D; de Santis, D; Calabrese, C; Cacciatore, F; Gargiulo, G; Ferrara, N; Rengo, G; Sica, V; Napoli, C; Rengo, F

    2005-01-01

    Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus. PMID:15664731

  7. Fusion Pore Size Limits 5-HT Release From Single Enterochromaffin Cell Vesicles.

    PubMed

    Raghupathi, Ravinarayan; Jessup, Claire F; Lumsden, Amanda L; Keating, Damien J

    2016-07-01

    Enterochromaffin cells are the major site of serotonin (5-HT) synthesis and secretion providing ∼95% of the body's total 5-HT. 5-HT can act as a neurotransmitter or hormone and has several important endocrine and paracrine roles. We have previously demonstrated that EC cells release small amounts of 5-HT per exocytosis event compared to other endocrine cells. We utilized a recently developed method to purify EC cells to demonstrate the mechanisms underlying 5-HT packaging and release. Using the fluorescent probe FFN511, we demonstrate that EC cells express VMAT and that VMAT plays a functional role in 5-HT loading into vesicles. Carbon fiber amperometry studies illustrate that the amount of 5-HT released per exocytosis event from EC cells is dependent on both VMAT and the H(+)-ATPase pump, as demonstrated with reserpine or bafilomycin, respectively. We also demonstrate that increasing the amount of 5-HT loaded into EC cell vesicles does not result in an increase in quantal release. As this indicates that fusion pore size may be a limiting factor involved, we compared pore diameter in EC and chromaffin cells by assessing the vesicle capture of different-sized fluorescent probes to measure the extent of fusion pore dilation. This identified that EC cells have a reduced fusion pore expansion that does not exceed 9 nm in diameter. These results demonstrate that the small amounts of 5-HT released per fusion event in EC cells can be explained by a smaller fusion pore that limits 5-HT release capacity from individual vesicles. PMID:26574734

  8. Observations on the site and mode of action of pyrogens in the rabbit brain

    PubMed Central

    Cooper, K. E.; Cranston, W. I.; Honour, A. J.

    1967-01-01

    1. Leucocyte pyrogen has been injected bilaterally into various parts of the rabbit brain. It caused fever when injected into the pre-optic area and the anterior hypothalamus, but not when injected into the posterior hypothalamus, the mid-brain, the pons, the cerebellum or the cerebral cortex. 2. The mean time which elapsed between a leucocyte pyrogen injection into the anterior hypothalamus and the onset of fever was 7·8 min. For similar injections of bacterial pyrogen the time lag was 24·8 min. The mean time lag between bilateral injections of noradrenaline into the anterior hypothalamus and the onset of fever was 7·4 min. 3. The amount of leucocyte pyrogen required to cause fever when injected into the anterior hypothalamus was less than 1/100 of that required to cause a similar fever on intravenous injection. The quantity of bacterial pyrogen injected into the hypothalamus was of the same order as that which would cause a similar fever on intravenous injection. 4. Control injections of saline, plasma, cerebrospinal fluid, heated leucocyte pyrogen and red cells into the anterior hypothalamus did not cause fever. 5. After attempts to deplete the hypothalamus of its monoamine stores by intraventricular injections of reserpine, the rabbit had fever as a result of an intravenous injection of bacterial pyrogen. 6. We conclude that the anterior hypothalamus and the pre-optic area are sites at which leucocyte pyrogen acts to cause fever in the rabbit. The mechanism of this febrile response is not clear, but it appears that part, at least, of the response could be mediated by a mechanism other than release of noradrenaline or failure to release 5-HT. ImagesPlate 1 PMID:6050108

  9. Neuroprotective potential of Beta vulgaris L. in Parkinson's disease

    PubMed Central

    Nade, Vandana S.; Kawale, Laxman A.; Zambre, Shankar S.; Kapure, Amit B.

    2015-01-01

    Objective: The objective was to investigate the neuroprotective role of Beta vulgaris in Parkinson's disease (PD). Materials and Methods: PD was induced by administration of reserpine (5 mg/kg/day, i.p for 5 consecutive days), haloperidol (1 mg/kg, i.p.), and tacrine (2.5 mg/kg, i.p.) in experimental animals. The symptoms of PD such as tremors, akinesia, rigidity, catalepsy, and vacuous chewing movements (VCMs) were evaluated. Foot shock-induced aggression (FSIA) model was used to confirm anti-parkinsonian activity. The methanolic extract of Beta vulgaris (MEBV) was administered at doses of 100, 200, and 300 mg/kg, p.o. The combination of L-dopa and carbidopa was used as a standard drug. Behavioral studies such as locomotor activity and grip strength were determined, and oxidative stress was evaluated in FSIA model in rat brain. Results: Pretreatment with MEBV (200 and 300 mg/kg) significantly reduced the intensity of muscular rigidity, duration of catalepsy, akinesia, the number of tremors, VCMs, and increase fighting behavior. The locomotor activity and grip strength were significantly increased by MEBV. In FSIA, the biochemical analysis of brain revealed the increased level of lipid peroxidation (LPO) and decreased levels of superoxide dismutase (SOD) and catalase (CAT). MEBV significantly reduced LPO level and restored the defensive antioxidant enzymes SOD and CAT in rat brain. Conclusions: The results indicated the protective role of B. vulgaris against PD. The mechanism of protection may be due to augmentation of cellular antioxidants. PMID:26288473

  10. Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum.

    PubMed

    Harsing, L G; Sershen, H; Lajtha, A

    1994-01-01

    We measured the effect of ibogaine on the tritium efflux from isolated mouse striatum preloaded with [3H]dopamine ([3H]DA). Ibogaine increased the basal tritium outflow in a concentration-dependent manner, but it was without effect on electrical stimulation-induced tritium overflow. Separation of the released radioactivity after ibogaine administration showed that this drug increased the release of [3H]DA and [3H]-dihydroxyphenylacetic acid ([3H]DOPAC), but the efflux of O-methylated-deaminated metabolites was not changed. The dopamine (DA)-releasing effect of ibogaine was reduced by the DA uptake inhibitors cocaine and nomifensine. The tritium efflux evoked by ibogaine was not altered by omission of Ca2+ from the perfusion buffer or by inhibition of the voltage-sensitive Na+ channels with tetrodotoxin. Ibogaine maintained its effect on release from superfused striatum prepared from reserpine-pretreated mice. The ibogaine-induced tritium release measured from mouse striatum that was preloaded with [3H]DA was not affected by the D-2 DA receptor ligands (-)-quinpirole and (+/-)-sulpiride, indicating that the ibogaine-induced release is not subject to presynaptic autoreceptor regulation. Ibogaine failed to affect [3H]DA uptake and retention in mouse striatum. These data indicate that at the nerve terminal level ibogaine releases DA, and the primary source for the release is probably the cytoplasmic pool. The DA-releasing effect of ibogaine may have importance in mediation of its hallucinogenic action, as seen in a frequent practice in African cults. PMID:7826572