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Sample records for adrenergic nerve terminals

  1. Opioid receptor types on adrenergic nerve terminals of rabbit ear artery.

    PubMed Central

    Fukuda, H.; Hosoki, E.; Ishida, Y.; Moritoki, H.

    1985-01-01

    Methionine enkephalin, leucine enkephalin, [D-Ala2, D-Leu5] enkephalin, alpha-neoendorphin, beta-endorphin, dynorphin (1-13) and ethylketocyclazocine inhibited the contractions of rabbit ear artery ring segments elicited by transmural nerve stimulation at 8 Hz. Ethylketocyclazocine, dynorphin (1-13) and leucine enkephalin produced partial inhibition, their apparent intrinsic activities (alpha) being 0.57, 0.75 and 0.66, respectively. Morphine and normorphine, which are agonists at mu-receptors, did not inhibit the response of the artery. Naloxone antagonized the actions of opioids and ethylketocyclazocine, and was more effective against methionine enkephalin, leucine enkephalin and [D-Ala2, D-Leu5] enkephalin than against alpha-neoendorphin, ethylketocyclazocine and dynorphin (1-13). The pA2 values of naloxone against so-called delta-agonists were approx. 8.5, and against so-called kappa-agonists were approx. 7.7. The supposed kappa-antagonist, Mr2266, was more effective than naloxone in antagonizing the actions of alpha-neoendorphin, and the kappa-agonists dynorphin (1-13) and ethylketocyclazocine. The pA2 values of Mr2266 against kappa-agonists were 8.5-9.0, and against delta-agonists were 7.8 or less. The opioid peptides and opioids tested did not cause dilatation of the artery previously contracted with histamine. These results suggest that the opioid peptides and ethylketocyclazocine acted on opioid receptors at adrenergic nerve terminals in the ear artery. The opioid receptors appear to be of the delta- and kappa-types, not the mu-type. PMID:2998521

  2. Topical administration of adrenergic receptor pharmaceutics and nerve growth factor

    PubMed Central

    Steinle, Jena J

    2010-01-01

    Topical application of nerve growth factor (NGF) and adrenergic receptor pharmaceutics are currently in use for corneal ulcers and glaucoma. A recent interest in the neuroprotective abilities of NGF has led to a renewed interest in NGF as a therapeutic for retinal and choroidal diseases. NGF can promote cell proliferation through actions of the TrkA receptor or promote apoptosis through receptor p75NTR. This understanding has led to novel interest in the role of NGF for diseases of the posterior eye. The role of β-adrenergic receptor agonists and antagonists for treatments of glaucoma, diabetic retinopathy, and their potential mechanisms of action, are still under investigation. This review discusses the current knowledge and applications of topical NGF and adrenergic receptor drugs for ocular disease. PMID:20668722

  3. Mechanism of nicotine-induced release of noradrenaline from adrenergic nerve endings

    PubMed Central

    Jayasundar, S.; Vohra, M.M.

    1977-01-01

    1 A study of the mechanism of release of [3H]-noradrenaline ([3H]-NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition. 2 Nicotine (20 μg/ml)-induced release of [3H]-NA was significantly potentiated in K+-free Krebs solution as compared to that in normal Krebs-Ringer solution. 3 Nicotine-induced release of [3H]-NA was significantly reduced in Na+-deficient Krebs solution (containing only 11 mM Na+) and was abolished in Na+-free Krebs solution. 4 In totally depolarized tissues, nicotine failed to cause an outflow of [3H]-NA but Ca2+ (5 mM) did so. 5 Nicotine required the presence of Ca2+ in the incubation medium to cause release of [3H]-NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca2+. 6 Nicotine-induced release of [3H]-NA was demonstrated in high Ca2+, Na+-free Krebs solution in which all Na+ had been replaced with Ca2+. 7 It is concluded that nicotine increases the membrane permeability to both Na+ and Ca2+. It is also suggested that the increase in permeability to Ca2+ alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings. PMID:922247

  4. Electrophysiology of corneal cold receptor nerve terminals.

    PubMed

    Carr, Richard W; Brock, James A

    2002-01-01

    The mechanisms of sensory transduction in the fine nerve terminals of free nerve endings supplied by Adelta and C sensory axons are largely a matter of speculation. This is because the nerve terminals are small and inaccessible, particularly in intact tissues like skin. However, some of the difficulties associated with investigating the physiology of fine nerve terminals have recently been overcome using an in vitro preparation of the guinea-pig cornea that allows nerve terminal impulses (NTIs) to be recorded extracellularly from single polymodal and cold receptor nerve terminals. For cold receptors, the rate of spontaneously occurring NTIs is increased during cooling and decreased during heating. In addition, heating and cooling differentially modulate the shape of the recorded NTI. At the same temperature, NTIs are larger in amplitude and faster in time course during heating than those during cooling. The differential effect of heating and cooling on NTI shape is not considered to result simply from the temperature dependence of voltage-activated conductance kinetics or activity dependent changes in membrane excitability. Instead, changes in NTI shape may reflect changes in nerve terminal membrane potential that underlie the process of thermal transduction.

  5. Activity of the Adrenergic Nerve System in the Airways Permeability of Healthy Persons

    PubMed Central

    Gashi, Njazi; Islami, Pëllumb; Mustafa, Lirim; Maloku, Halit; Veseli, Arta; Islami, Hilmi

    2013-01-01

    Objective: In this work, role of the adrenergic nerve system (alpha1 and beta2) in adjustment of the bronchomotor tonus in healthy people was researched. Methods: Parameters of the lung function are determined by Body plethysmography. Raw and ITGV were registered and SRaw was calculated as well. Aerosolization is done with standard aerosolizing machines – Asema. Results: Results gained shows that following the blockade of beta-2 adrenergic receptor with Propranolol (20 mg–aerosol), stimulation of alpha adrenergic receptor with Oxedrine (120 mg-aerosol) and blockage of these receptors with Tolazoline (20 mg-aerosol), does not change significantly the bronchomotor tonus of the tracheobronchial tree (p > 0.1). Meanwhile, stimulation of the beta-2 adrenergic receptor with Hexoprenaline (2 inh × 0.2 mg) is associated with a significant increase of the peripheral resistance of the airways (p < 0.01). Conclusion: This suggests that the activity of the alpha1-adrenergic receptor, unlike the activity of the beta2-adrenergic receptor in the healthy people smooth musculature, is not significant and as such is insufficient to oppose to the tonic activities of the cholinergic system. PMID:24554803

  6. Adrenergic vasoconstriction in peripheral nerves of the rabbit

    SciTech Connect

    Selander, D.; Mansson, L.G.; Karlsson, L.; Svanvik, J.

    1985-01-01

    The blood flow in the sciatic nerve of the rabbit was estimated from the wash out of intraneurally injected /sup 133/Xe. To avoid diffusion of the tracer into the surrounding muscular tissue, the nerve was covered by a gas-tight plastic film. Using this technique, the basal blood flow in the sciatic nerve was estimated to 35 ml X min-1 X 100 g-1. It was found that intraarterial norepinephrine and electrical stimulation of the lumbar sympathetic chain strongly reduced the wash out of /sup 133/Xe, which only can be explained by a pronounced reduction of the blood flow in the nerve itself. The blood flow again increased within 4 min of stopping the infusion of norepinephrine or the sympathetic stimulation. The prolonged effect and higher neurotoxicity of local anesthetics containing adrenaline may be explained by an alpha receptor-mediated vasoconstriction of the microvessels of peripheral nerves.

  7. Central beta-adrenergic receptors mediate renal nerve activity during stress in conscious spontaneously hypertensive rats.

    PubMed

    Koepke, J P; DiBona, G F

    1985-01-01

    The effects of intracerebroventricular (i.c.v.) administration of beta-adrenergic receptor antagonists (d,l-propranolol or timolol, 30 micrograms in 2 microL of isotonic saline) on the increased renal sympathetic nerve activity and decreased urinary sodium excretion (UNaV) responses to stressful environmental stimulation (air jet to head) in conscious spontaneously hypertensive rats (SHR) were examined. Before i.c.v. d,l-propranolol or timolol, air stress increased renal activity (68% from 10.6 +/- 2.1 and 63% from 8.2 +/- 0.9 integrator resets/min respectively). In contrast, after i.c.v. d,l-propranolol or timolol in the same conscious SHR, air stress had no effect on renal sympathetic nerve activity (+7% from 8.1 +/- 1.7 and +7% from 5.5 +/- 1.0 integrator resets/min respectively). Air stress decreased UNaV in conscious SHR given i.c.v. saline vehicle (25% from 2.8 +/- 0.5 microEq/min/100 g body weight), but had no effect on effective renal plasma flow or glomerular filtration rate. In contrast, after i.c.v. d,l-propranolol or timolol, air stress had no effect on UNaV (0% from 2.8 +/- 0.5 and +9% from 3.3 +/- 0.3 microEq/min/100 g body weight respectively). Mean arterial pressure increased similarly during air stress with i.c.v. saline-vehicle or beta-adrenergic receptor antagonists. Intravenous administration of the same doses of d,l-propranolol or timolol did not prevent the increased renal sympathetic nerve activity or decreased UNaV responses resulting from air stress. These results suggest that central nervous system beta-adrenergic receptors mediate the increased renal sympathetic nerve activity and decreased UNaV responses resulting from stressful environmental stimulation in conscious SHR.

  8. [Changes in adrenergic nerve plexuses of the heart during immobilization stress in the rat].

    PubMed

    Mar'ian, K L; Buniatian, A M

    1984-03-01

    Luminescent microscopical analysis on the state of the cardiac adrenergic neural apparatus under immobilization stress has been performed in 48 rats of August and Wistar strains. The rats of August strain demonstrate a high sensitivity to the stress: 40% of the animals died during the first 4-17 h of immobilization. Cryostate sections are treated in 2% glyoxylic acid and studied in the luminescent microscope. Quantitative analysis of density distribution of the adrenergic neural terminals is performed by means of dot nets. Decreasing luminescent brightness and decreasing density by 10-15% are noted in the right auricle, and by 30-34%--in the left ventricle, comparing to that of the control. In the animals died a sudden death these parameters are even stronger (28% and 54%, respectively). The data obtained correlate to the functional disturbances of the heart activity (fluctuations of the arterial pressure, disturbances of the rhythm, ECG changes). A suggestion is made that catecholamines content in the neural terminals of the heart is of certain importance in development of the cardiovascular disturbances under immobilization stress.

  9. Ionic channels and hormone release from peptidergic nerve terminals.

    PubMed

    Lemos, J R; Nordmann, J J

    1986-09-01

    Although there is considerable evidence that depolarization of nerve cell terminals leads to the entry of Ca2+ and to the secretion of neurohormones and neurotransmitters, the details of how ionic currents control the release of neuroactive substances from nerve terminals are unknown. The small size of most nerve terminals has precluded direct analysis of membrane ionic currents and their influence on secretion. We now report that it is possible, using patch-clamp techniques, to study stimulus--secretion coupling in isolated peptidergic nerve terminals. Sinus gland terminals from Cardisoma are easily isolated following collagenase treatment and appear morphologically and electrically very similar to non-dissociated nerve endings. We have observed two types of single-channel currents not previously described. The first ('f') channel is activated by intracellular Na+ and the second ('s') by intracellular Ca2+. Both show little selectivity between Na+ and K+. In symmetrical K+, these cation channels have mean conductances of 69 and 213 pS, respectively. Furthermore, at least three types of Ca2+ channels can be reconstituted from nerve terminal membranes prepared from sinus glands. Nerve terminals can also be isolated from the rat neural lobe. These neurosecretosomes release oxytocin and vasopressin, in response to membrane depolarization, only in the presence of external Ca2+. The depolarization of the nerve endings is associated with an increase in intracellular free Ca2+ concentration and this increase, measured using a fluorescent indicator, is abolished by Ca2+ channel blockers. Channels similar in their properties to the f and s channels also exist in rat neural lobe endings. Since these channels have not been found in other neurones or neuronal structures they may be unique to peptidergic nerve terminals.

  10. Synaptic vesicle generation from central nerve terminal endosomes.

    PubMed

    Kokotos, Alexandros C; Cousin, Michael A

    2015-03-01

    Central nerve terminals contain a small number of synaptic vesicles (SVs) that must sustain the fidelity of neurotransmission across a wide range of stimulation intensities. For this to be achieved, nerve terminals integrate a number of complementary endocytosis modes whose activation spans the breadth of these neuronal stimulation patterns. Two such modes are ultrafast endocytosis and activity-dependent bulk endocytosis, which are triggered by stimuli at either end of the physiological range. Both endocytosis modes generate endosomes directly from the nerve terminal plasma membrane, before the subsequent production of SVs from these structures. This review will discuss the current knowledge relating to the molecular mechanisms involved in the generation of SVs from nerve terminal endosomes, how this relates to other mechanisms of SV production and the functional role of such SVs.

  11. Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure.

    PubMed Central

    Robinette, J B; Conger, J D

    1990-01-01

    The roles of intrarenal angiotensin (A) and thromboxane (TX) in the vascular hypersensitivity to renal nerve stimulation (RNS) and paradoxical vasoconstriction to renal perfusion pressure (RPP) reduction in the autoregulatory range in 1 wk norepinephrine (NE)-induced acute renal failure (ARF) in rats were investigated. Renal blood flow (RBF) responses were determined before and during intrarenal infusion of an AII and TXA2 antagonist. Saralasin or SQ29548 alone partially corrected the slopes of RBF to RNS and RPP reduction in NE-ARF rats (P less than 0.02). Saralasin + SQ29548 normalized the RBF response to RNS. While combined saralasin + SQ29548 eliminated the vasoconstriction to RPP reduction, similar to the effect of renal denervation, appropriate vasodilatation was not restored. Renal vein norepinephrine efflux during RNS was disproportionately increased in NE-ARF (P less than 0.001) and was suppressed by saralasin + SQ29548 infusion (P less than 0.005). It is concluded that the enhanced sensitivity to RNS and paradoxical vasoconstriction to RPP reduction in 1 wk NE-ARF kidneys are the result of intrarenal TX and AII acceleration of neurotransmitter release to adrenergic nerve activity. PMID:2243129

  12. Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus

    PubMed Central

    Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

    2013-01-01

    Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (−)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries. PMID:23668336

  13. Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus.

    PubMed

    Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

    2013-07-01

    Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (-)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries.

  14. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries.

  15. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    PubMed

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-01

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries. PMID:26671004

  16. Multiple cytosolic calcium buffers in posterior pituitary nerve terminals.

    PubMed

    McMahon, Shane M; Chang, Che-Wei; Jackson, Meyer B

    2016-03-01

    Cytosolic Ca(2+) buffers bind to a large fraction of Ca(2+) as it enters a cell, shaping Ca(2+) signals both spatially and temporally. In this way, cytosolic Ca(2+) buffers regulate excitation-secretion coupling and short-term plasticity of release. The posterior pituitary is composed of peptidergic nerve terminals, which release oxytocin and vasopressin in response to Ca(2+) entry. Secretion of these hormones exhibits a complex dependence on the frequency and pattern of electrical activity, and the role of cytosolic Ca(2+) buffers in controlling pituitary Ca(2+) signaling is poorly understood. Here, cytosolic Ca(2+) buffers were studied with two-photon imaging in patch-clamped nerve terminals of the rat posterior pituitary. Fluorescence of the Ca(2+) indicator fluo-8 revealed stepwise increases in free Ca(2+) after a series of brief depolarizing pulses in rapid succession. These Ca(2+) increments grew larger as free Ca(2+) rose to saturate the cytosolic buffers and reduce the availability of Ca(2+) binding sites. These titration data revealed two endogenous buffers. All nerve terminals contained a buffer with a Kd of 1.5-4.7 µM, and approximately half contained an additional higher-affinity buffer with a Kd of 340 nM. Western blots identified calretinin and calbindin D28K in the posterior pituitary, and their in vitro binding properties correspond well with our fluorometric analysis. The high-affinity buffer washed out, but at a rate much slower than expected from diffusion; washout of the low-affinity buffer could not be detected. This work has revealed the functional impact of cytosolic Ca(2+) buffers in situ in nerve terminals at a new level of detail. The saturation of these cytosolic buffers will amplify Ca(2+) signals and may contribute to use-dependent facilitation of release. A difference in the buffer compositions of oxytocin and vasopressin nerve terminals could contribute to the differences in release plasticity of these two hormones.

  17. Comparison of bretylium and guanethidine: tolerance, and effects on adrenergic nerve function and responses to sympathomimetic amines

    PubMed Central

    Boura, A. L. A.; Green, A. F.

    1962-01-01

    Bretylium depresses the slope of regression lines relating frequency of sympathetic nerve stimulation to magnitude of contractions of the cat nictitating membrane. In contrast, guanethidine and reserpine preferentially abolish responses to low rates of nerve stimulation and cause a roughly parallel shift of the regression lines. The hypersensitivity of the nictitating membranes of cats to intravenous adrenaline or noradrenaline is far greater after a series of small daily doses of bretylium or guanethidine than after single large doses. The maximal sensitivity produced was similar to that after postganglionic sympathetic nerve section and exceeded that produced by ganglion blockade. The development of hypersensitivity to catechol amines is accompanied by some return of responses of the nictitating membranes to sympathetic nerve stimulation despite continued daily administration of bretylium or guanethidine. In cats given bretylium daily, responses to low rates of nerve stimulation become greater than in controls unless the dose of bretylium given subcutaneously is 50 mg/kg or more. When marked hypersensitivity to catechol amines has been produced by giving bretylium or guanethidine daily for 7 or 14 days, the sympathomimetic effects of these compounds are greater. Responses to intravenous dimethylphenylpiperazinium are also increased and the results suggest that even large daily doses of adrenergic neurone blocking agents do not appreciably impair the functioning of the adrenal medulla. The pressor effects of intravenous adrenaline, noradrenaline and dimethylphenylpiperazinium iodide increase less than the corresponding nictitating membrane responses. These results are discussed in relation to tolerance to adrenergic neurone blockade, and differences between the effects of bretylium and guanethidine found in man. Bretylium and guanethidine depress the slopes of the dose-response curves for the pressor and nictitating membrane contracting effects of tyramine. When

  18. N-terminal {beta}{sub 2}-adrenergic receptor polymorphisms do not correlate with bronchodilator response in asthma families

    SciTech Connect

    Holyroyd, K.J.; Dragwa, C.; Xu, J.

    1994-09-01

    Family and twin studies have suggested that susceptibility to asthma is inherited. One clinically relevant phenotype in asthma is the bronchodilator response to beta adrenergic therapy (reversibility) which may also be inherited and vary among asthmatics. Two polymorphisms of the {beta}{sub 2}-adrenergic receptor common to both asthmatic and normal individuals have been reported. One polymorphism, an amino acid polymorphism at position 16, correlated in one study with the need for long-term corticosteriod use in a population of asthmatics. It is conceivable that the increased use of corticosteroids needed to control symptoms in these patients may be explained by a decreased responsiveness to brochodilators mediated through this amino acid polymorphism in the {beta}{sub 2}-adrenergic receptor. However, the response to {beta}{sub 2} bronchodilators was not tested in these patients. In our Dutch asthma families, DNA sequencing of the {beta}{sub 2}-adrenergic receptor has been performed for N-terminal polymorphisms at amino acid positions 16 and 27 in over 100 individuals, and no correlation was found with the increase of FEV{sub 1} in response to bronchodilator. Linkage analysis between bronchodilator response and marker D5S412 near the {beta}{sub 2}-adrenergic receptor gene was performed in 286 sibpairs from these families. Using a bronchodilator response of >10% in FEV{sub 1} as a qualitative definition of affected individuals, there were 145 unaffected sibpairs, 121 sibpairs where one was affected, and 20 in which both were affected. Linear regression analysis of these sibpair data suggested possible linkage (p=0.007). This supports further examination of the {beta}{sub 2}-adrenergic receptor and its regulatory regions for polymorphisms that correlate with the bronchodilator response in asthma families.

  19. Multiple cytosolic calcium buffers in posterior pituitary nerve terminals.

    PubMed

    McMahon, Shane M; Chang, Che-Wei; Jackson, Meyer B

    2016-03-01

    Cytosolic Ca(2+) buffers bind to a large fraction of Ca(2+) as it enters a cell, shaping Ca(2+) signals both spatially and temporally. In this way, cytosolic Ca(2+) buffers regulate excitation-secretion coupling and short-term plasticity of release. The posterior pituitary is composed of peptidergic nerve terminals, which release oxytocin and vasopressin in response to Ca(2+) entry. Secretion of these hormones exhibits a complex dependence on the frequency and pattern of electrical activity, and the role of cytosolic Ca(2+) buffers in controlling pituitary Ca(2+) signaling is poorly understood. Here, cytosolic Ca(2+) buffers were studied with two-photon imaging in patch-clamped nerve terminals of the rat posterior pituitary. Fluorescence of the Ca(2+) indicator fluo-8 revealed stepwise increases in free Ca(2+) after a series of brief depolarizing pulses in rapid succession. These Ca(2+) increments grew larger as free Ca(2+) rose to saturate the cytosolic buffers and reduce the availability of Ca(2+) binding sites. These titration data revealed two endogenous buffers. All nerve terminals contained a buffer with a Kd of 1.5-4.7 µM, and approximately half contained an additional higher-affinity buffer with a Kd of 340 nM. Western blots identified calretinin and calbindin D28K in the posterior pituitary, and their in vitro binding properties correspond well with our fluorometric analysis. The high-affinity buffer washed out, but at a rate much slower than expected from diffusion; washout of the low-affinity buffer could not be detected. This work has revealed the functional impact of cytosolic Ca(2+) buffers in situ in nerve terminals at a new level of detail. The saturation of these cytosolic buffers will amplify Ca(2+) signals and may contribute to use-dependent facilitation of release. A difference in the buffer compositions of oxytocin and vasopressin nerve terminals could contribute to the differences in release plasticity of these two hormones. PMID:26880753

  20. Multiple cytosolic calcium buffers in posterior pituitary nerve terminals

    PubMed Central

    McMahon, Shane M.; Chang, Che-Wei

    2016-01-01

    Cytosolic Ca2+ buffers bind to a large fraction of Ca2+ as it enters a cell, shaping Ca2+ signals both spatially and temporally. In this way, cytosolic Ca2+ buffers regulate excitation-secretion coupling and short-term plasticity of release. The posterior pituitary is composed of peptidergic nerve terminals, which release oxytocin and vasopressin in response to Ca2+ entry. Secretion of these hormones exhibits a complex dependence on the frequency and pattern of electrical activity, and the role of cytosolic Ca2+ buffers in controlling pituitary Ca2+ signaling is poorly understood. Here, cytosolic Ca2+ buffers were studied with two-photon imaging in patch-clamped nerve terminals of the rat posterior pituitary. Fluorescence of the Ca2+ indicator fluo-8 revealed stepwise increases in free Ca2+ after a series of brief depolarizing pulses in rapid succession. These Ca2+ increments grew larger as free Ca2+ rose to saturate the cytosolic buffers and reduce the availability of Ca2+ binding sites. These titration data revealed two endogenous buffers. All nerve terminals contained a buffer with a Kd of 1.5–4.7 µM, and approximately half contained an additional higher-affinity buffer with a Kd of 340 nM. Western blots identified calretinin and calbindin D28K in the posterior pituitary, and their in vitro binding properties correspond well with our fluorometric analysis. The high-affinity buffer washed out, but at a rate much slower than expected from diffusion; washout of the low-affinity buffer could not be detected. This work has revealed the functional impact of cytosolic Ca2+ buffers in situ in nerve terminals at a new level of detail. The saturation of these cytosolic buffers will amplify Ca2+ signals and may contribute to use-dependent facilitation of release. A difference in the buffer compositions of oxytocin and vasopressin nerve terminals could contribute to the differences in release plasticity of these two hormones. PMID:26880753

  1. Extension of synaptic extracellular matrix during nerve terminal sprouting in living frog neuromuscular junctions.

    PubMed

    Chen, L; Ko, C P

    1994-02-01

    Remodeling of the synaptic extracellular matrix (ECM) and its dynamic relationship with nerve terminal plasticity have been demonstrated in normal frog neuromuscular junctions (NMJs) in vivo (Chen et al., 1991). Our previous work has led to a hypothesis that extension of synaptic ECM precedes nerve terminal growth during synaptic remodeling. To test this hypothesis, the present study examined the changes of synaptic ECM in frog NMJs that were primarily undergoing nerve terminal growth and sprouting. Frog sartorius muscles were double stained with a fluorescent nerve terminal dye (4-Di-2-Asp) and rhodamine-tagged peanut agglutinin (PNA), which recognizes synaptic ECM. The double-labeled NMJs were visualized in vivo with video-enhanced fluorescence microscopy. Nerve sprouting was then induced in the muscle by grafting segments of the contralateral sciatic nerve. The identified NMJs were restrained and reexamined 2-3 months later. Extensive sprouting was observed in 46% of 167 identified NMJs. At junctional regions that showed extension or formation of new branches, synaptic ECM was commonly seen to have the same shape and distribution as the nerve terminal. However, extension of synaptic ECM beyond the corresponding nerve terminals, often by tens of microns, was observed in 29% of these newly formed junctional regions. This lack of correlation might be transient, as growth of nerve terminals following extended, PNA-stained ECM was seen. Examination with histological staining not only confirmed a lack of nerve terminal at the extended synaptic ECM region but also indicated an absence of AChE and postsynaptic junctional folds. The absence of these postsynaptic specializations at the extended, PNA-stained ECM region makes it unlikely that this region was previously occupied by nerve terminals that had retracted. Thus, the present study provides further findings consistent with the hypothesis that synaptic ECM precedes nerve terminal outgrowth and that the extension of

  2. Strontium, barium, and manganese metabolism in isolated presynaptic nerve terminals

    SciTech Connect

    Rasgado-Flores, H.; Sanchez-Armass, S.; Blaustein, M.P.; Nachshen, D.A.

    1987-06-01

    To gain insight into the mechanisms by which the divalent cations Sr, Ba, and Mn affect neurotransmitter release from presynaptic nerve terminals, the authors examined the sequestration of these cations, ion comparison to Ca, by mitochondrial and nonmitochondrial organelles and the extrusion of these cations from isolated nerve terminals. Sequestration was studied in synaptosomes made leaky to small ions by treatment with saponin; efflux was examined in intact synaptosomes that were preloaded with the divalent cations by incubation in depolarizing (K rich) media. The selectivity sequence for ATP-dependent mitochondrial uptake that they observed was Mn>>Ca>Sr>>Ba, whereas that for the SER was Ca greater than or equal to Mn>Sr>>Ba. When synaptosomes that were preloaded with divalent cations were incubated in Na- and Ca-free media, there was little efflux of /sup 45/Ca, /sup 133/Ba, /sup 85/Sr, or /sup 54/Mn. When the incubation was carried out in media containing Na without Ca, there was substantial stimulation of Ca and Sr efflux, but only slight stimulation of Ba or Mn efflux. In Na-free media, the addition of 1 mM Ca promoted the efflux of all four divalent cations, probably via Ca-divalent cation exchange. In summary, the sequestration and extrusion data suggest that, with equal loads, Mn will be buffered to the greatest extent, whereas Ba will be least well buffered. These results may help to explain why Mn has a very long-lasting effect on transmitter release, while the effect of Sr is much briefer.

  3. Insights into β2-adrenergic receptor binding from structures of the N-terminal lobe of ARRDC3.

    PubMed

    Qi, Shiqian; O'Hayre, Morgan; Gutkind, J Silvio; Hurley, James H

    2014-12-01

    ARRDC3 is one of six known human α-arrestins, and has been implicated in the downregulation of the β2-adrenergic receptor (β2AR). ARRDC3 consists of a two-lobed arrestin fold and a C-terminal tail containing two PPYX motifs. In the current model for receptor downregulation by ARRDC3, the arrestin fold portion is thought to bind the receptor, while the PPXY motifs recruit ubiquitin ligases of the NEDD4 family. Here we report the crystal structures of the N-terminal lobe of human ARRDC3 in two conformations, at 1.73 and 2.8 Å resolution, respectively. The structures reveal a large electropositive region that is capable of binding phosphate ions of crystallization. Residues within the basic patch were shown to be important for binding to β2AR, similar to the situation with β-arrestins. This highlights potential parallels in receptor recognition between α- and β-arrestins.

  4. The effects of inorganic particles of lunar soil simulant on brain nerve terminals

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Sivko, Roman; Borisov, Arseniy

    2012-07-01

    The health effects from lunar soil exposure are almost completely unknown, whereas the observations suggest that it can be deleterious to human physiology. It is important that the components of lunar soil may be internalized with lipid fractions of the lung epithelium, which in turn may help ions to overcome the blood-brain barrier. The study focused on the effects of JSC-1a Lunar Soil Simulant (LSS) (Orbital Technologies Corporation, Madison, USA) on rat brain nerve terminals (synaptosomes). We revealed that brain nerve terminals were not indifferent to the exposure to LSS inorganic particles. Using Zetasizer Nanosystem (Malvern Instruments) with helium-neon laser for dynamic light scattering (DLS), the synaptosomal size before and after the addition of LSS was measured and the binding of LSS inorganic particles to nerve terminals was demonstrated. Using potential-sensitive fluorescent dye rhodamine 6G, we showed that LSS inorganic particles did not influence the potential of the plasma membrane of nerve terminals. Acidification of synaptic vesicles of nerve terminals did not change in the presence of LSS inorganic particles that was revealed with pH-sensitive fluorescent dye acridine orange. However, LSS inorganic particles influenced accumulation of glutamate, the main excitatory neurotransmitter in the CNS, by nerve terminals. Thus, we report that inorganic particles of LSS influence accumulation of glutamate in brain nerve terminals and this fact may have harmful consequences to human physiology, in particular glutamate homeostasis in the mammalian CNS.

  5. Molecular Insights into the Dynamics of Pharmacogenetically Important N-Terminal Variants of the Human β2-Adrenergic Receptor

    PubMed Central

    Sengupta, Durba; Joshi, Manali

    2014-01-01

    The human β2-adrenergic receptor (β2AR), a member of the G-protein coupled receptor (GPCR) family, is expressed in bronchial smooth muscle cells. Upon activation by agonists, β2AR causes bronchodilation and relief in asthma patients. The N-terminal polymorphism of β2AR at the 16th position, Arg16Gly, has warranted a lot of attention since it is linked to variations in response to albuterol (agonist) treatment. Although the β2AR is one of the well-studied GPCRs, the N-terminus which harbors this mutation, is absent in all available experimental structures. The goal of this work was to study the molecular level differences between the N-terminal variants using structural modeling and atomistic molecular dynamics simulations. Our simulations reveal that the N-terminal region of the Arg variant shows greater dynamics than the Gly variant, leading to differential placement. Further, the position and dynamics of the N-terminal region, further, affects the ligand binding-site accessibility. Interestingly, long-range effects are also seen at the ligand binding site, which is marginally larger in the Gly as compared to the Arg variant resulting in the preferential docking of albuterol to the Gly variant. This study thus reveals key differences between the variants providing a molecular framework towards understanding the variable drug response in asthma patients. PMID:25501358

  6. Immunohistochemical study on the distribution and origin of GABAergic nerve terminals in the superior salivatory nucleus.

    PubMed

    Matsushima, Ayumi; Ichikawa, Hiroyuki; Fujita, Masako; Mitoh, Yoshihiro; Kobashi, Motoi; Yamashiro, Takashi; Matsuo, Ryuji

    2009-01-01

    The superior salivatory nucleus (SSN) is the primary parasympathetic center controlling submandibular salivatory secretion. Our previous electrophysiological study revealed that many SSN neurons receive GABAergic and glycinergic synaptic inputs. In the present study, we examined the distribution of GABAergic and glycinergic nerve terminals, GABA(A) receptors in the SSN, and the origin of GABAergic nerve terminals innervating the SSN. Glutamic acid decarboxylase (GAD) and glycine transporter 2 (GLYT2) were used as markers of GABAergic and glycinergic nerve terminals, respectively. GAD- and GLYT2-positive nerve terminals and GABA(A) receptors were examined immunohistochemically in SSN neurons labeled by the retrograde axonal transport of FastBlue (FB) injected into the chorda-lingual nerve. The SSN neurons abundantly contained GAD-positive nerve terminals and GABA(A) receptors, suggesting that SSN neurons undergo strong GABAergic inhibition. The origin of GABAergic terminals was examined in neurons labeled by the retrograde transport of FluoroGold (FG) injected into the SSN. GAD was used as a marker of GABAergic neurons. Numerous FG-labeled neurons were found in the forebrain and brainstem. However, in FG-labeled neurons, GAD-positive neurons were occasionally observed in the reticular formation of the brainstem. These findings suggest that SSN neurons mainly receive GABAergic projections from the reticular formation.

  7. Bladder contractions alter inspiratory termination by superior laryngeal and intercostal nerve stimulation.

    PubMed

    Bartlett, D; Knuth, S L

    1999-08-01

    Gradual distension of the urinary bladder evokes spontaneous bladder contractions (SBCs), which are associated with reduced inspiratory activity in the phrenic and other inspiratory motor nerves. We examined the influence of isovolumetric SBCs on the threshold for termination of phrenic inspiration by electrical stimulation of superior laryngeal and/or mid-thoracic intercostal nerves (ICN) in decerebrate, vagotomized, paralyzed, ventilated cats. Although SBCs reduced phrenic inspiratory activity, the threshold for inspiratory termination by nerve stimulation was increased. The results emphasize the complexity of the synaptic connections among brain stem neurons governing micturition and breathing.

  8. Triazines facilitate neurotransmitter release of synaptic terminals located in hearts of frog (Rana ridibunda) and honeybee (Apis mellifera) and in the ventral nerve cord of a beetle (Tenebrio molitor).

    PubMed

    Papaefthimiou, Chrisovalantis; Zafeiridou, Georgia; Topoglidi, Aglaia; Chaleplis, George; Zografou, Stella; Theophilidis, George

    2003-07-01

    Three triazine herbicides, atrazine, simazine and metribuzine, and some of their major metabolites (cyanuric acid and 6-azauracil) were investigated for their action on synaptic terminals using three different isolated tissue preparations from the atria of the frog, Rana ridibunda, the heart of the honeybee, Apis mellifera macedonica, and the ventral nerve cord of the beetle, Tenebrio molitor. The results indicate that triazines facilitate the release of neurotransmitters from nerve terminals, as already reported for the mammalian central nervous system. The no observed effect concentration, the maximum concentration of the herbicide diluted in the saline that has no effect on the physiological properties of the isolated tissue, was estimated for each individual preparation. According to their relative potency, the three triazines tested can be ranked as follows: atrazine (cyanuric acid), simazine>metribuzine (6-azauracil). The action of these compounds on the cholinergic (amphibians, insects), adrenergic (amphibian) and octopaminergic (insects) synaptic terminals is discussed.

  9. Different mechanisms of inhibition of nerve terminals by botulinum and snake presynaptic neurotoxins.

    PubMed

    Montecucco, Cesare; Rossetto, Ornella; Caccin, Paola; Rigoni, Michela; Carli, Luca; Morbiato, Laura; Muraro, Lucia; Paoli, Marco

    2009-10-01

    The different mode of action on peripheral nerve terminals of the botulinum neurotoxins and of the snake presynaptic phospholipase A2 neurotoxins is reviewed here. These two groups of toxins are highly toxic because they are neurospecific and at the same time are enzymes that can modify many substrate molecules before being inactivated. The similarity of symptoms they cause in humans derives from the fact that both botulinum neurotoxins (seven serotypes named A-G) and snake presynaptic PLA2 neurotoxins block the nerve terminals and that peripheral cholinergic terminals are major targets. Given this general similarity of targets and clinical symptoms, the specific molecular and cellular mechanisms at the basis of their action are very different. This difference appears evident from the beginning of intoxication, i.e. neurotoxins binding to peripheral nerve terminals and proceeds with the different site of actions and molecular targets.

  10. Morphology and Functional Anatomy of the Recurrent Laryngeal Nerve with Extralaryngeal Terminal Bifurcation

    PubMed Central

    Dogan, Sami

    2016-01-01

    Anatomical variations of the recurrent laryngeal nerve (RLN), such as an extralaryngeal terminal bifurcation (ETB), threaten the safety of thyroid surgery. Besides the morphology of the nerve branches, intraoperative evaluation of their functional anatomy may be useful to preserve motor activity. We exposed 67 RLNs in 36 patients. The main trunk, bifurcation point, and terminal branches of bifid nerves were macroscopically determined and exposed during thyroid surgery. The functional anatomy of the nerve branches was evaluated by intraoperative nerve monitoring (IONM). Forty-six RLNs with an ETB were intraoperatively exposed. The bifurcation point was located along the prearterial, arterial, and postarterial segments in 11%, 39%, and 50% of bifid RLNs, respectively. Motor activity was determined in all anterior branches. The functional anatomy of terminal branches detected motor activity in 4 (8.7%) posterior branches of 46 bifid RLNs. The motor activity in posterior branches created a wave amplitude at 25–69% of that in the corresponding anterior branches. The functional anatomy of bifid RLNs demonstrated that anterior branches always contained motor fibres while posterior branches seldom contained motor fibres. The motor activity of the posterior branch was weaker than that of the anterior branch. IONM may help to differentiate between motor and sensory functions of nerve branches. The morphology and functional anatomy of all nerve branches must be preserved to ensure a safer surgery. PMID:27493803

  11. Interaction of nanoparticles of ferric oxide with brain nerve terminals and blood platelets

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Sivko, Roman; Borisov, Arseniy

    2012-07-01

    Nanoparticles of ferric oxide are the components of Lunar and Martian soil simulants. The observations suggest that exposure to Lunar soli simulant can be deleterious to human physiology and the components of lunar soil may be internalized by lung epithelium and may overcome the blood-brain barrier. The study focused on the effects of nanoparticles of ferric oxide on the functional state of rat brain nerve terminals (synaptosomes) and rabbit blood platelets. Using photon correlation spectroscopy, we demonstrated the binding of nanoparticles of ferric oxide with nerve terminals and platelets. Nanoparticles did not depolarize the plasma membrane of nerve terminals and platelets that was shown by fluorimetry with potential-sensitive fluorescent dye rhodamine 6G. Using pH-sensitive fluorescent dye acridine orange, we revealed that the acidification of synaptic vesicles of nerve terminals and secretory granules of platelets did not change in the presence of nanoparticles. The initial velocity of uptake of excitatory neurotransmitter glutamate was not influenced by nanoparticles of ferric oxide, whereas glutamate binding to nerve terminals was altered. Thus, it was suggested that nanoparticles of ferric oxide might disturb glutamate transport in the mammalian CNS.

  12. Calpains participate in nerve terminal degeneration induced by spider and snake presynaptic neurotoxins.

    PubMed

    Duregotti, Elisa; Tedesco, Erik; Montecucco, Cesare; Rigoni, Michela

    2013-03-15

    α-latrotoxin and snake presynaptic phospholipases A2 neurotoxins target the presynaptic membrane of axon terminals of the neuromuscular junction causing paralysis. These neurotoxins display different biochemical activities, but similarly alter the presynaptic membrane permeability causing Ca(2+) overload within the nerve terminals, which in turn induces nerve degeneration. Using different methods, here we show that the calcium-activated proteases calpains are involved in the cytoskeletal rearrangements that we have previously documented in neurons exposed to α-latrotoxin or to snake presynaptic phospholipases A2 neurotoxins. These results indicate that calpains, activated by the massive calcium influx from the extracellular medium, target fundamental components of neuronal cytoskeleton such as spectrin and neurofilaments, whose cleavage is functional to the ensuing nerve terminal fragmentation.

  13. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals

    PubMed Central

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. PMID:27242505

  14. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals.

    PubMed

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission.

  15. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals.

    PubMed

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. PMID:27242505

  16. The effect of cold storage on the adrenergic mechanisms of intestinal smooth muscle

    PubMed Central

    Hattori, K.; Kurahashi, K.; Mori, J.; Shibata, S.

    1972-01-01

    1. In the guinea-pig taenia caecum, fluorescent adrenergic fibres terminate in both muscle layers. The density of these fibres is greater in the taenia than in the underlying circular muscle layer. The myenteric plexus and individual ganglion cells are also densely innervated by intensely fluorescent adrenergic nerve fibres. 2. After three days of cold storage, the specific fluorescence disappeared from all tissue layers of the taenia caecum and smooth muscle fibres. In contrast, cholinesterase active substances were still demonstrable in all tissue layers even after seven days of cold storage but the density of these substances was decreased. 3. Cold storage (3-7 days) decreased the tissue noradrenaline content and did not modify the cholinesterase enzyme activity (4 days). 4. In cold stored strips, the inhibitory response to nicotine, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) or electrical transmural stimulation was abolished and enhancement of the contractile response occurred. Cold storage also inhibited the inhibitory action of tyramine. Similar results were observed after reserpine treatment. 5. In fresh taenia, the relaxation produced by nicotine, DMPP and electrical transmural stimulation was inhibited by adrenoceptor blocking agents and bretylium. In cold storage preparations, contraction produced by these stimuli was blocked by parasympathetic blocking agents and potentiated by anti-cholinesterase. These results indicate that the inhibitory response to these stimulants is mediated by stimulation of the adrenergic nerve system more than by non-adrenergic nerves; the excitatory effect is probably due to stimulation of cholinergic nerves. 6. These results suggest that the adrenergic mechanisms of the taenia caecum are more labile in cold storage than the cholinergic mechanisms. Thus, the inhibitory action of cold storage on the relaxation produced by nicotine, DMPP, and transmural stimulation is probably explained by selective physical degeneration of

  17. Repetitive nerve stimulation transiently opens the mitochondrial permeability transition pore in motor nerve terminals of symptomatic mutant SOD1 mice.

    PubMed

    Nguyen, Khanh T; Barrett, John N; García-Chacón, Luis; David, Gavriel; Barrett, Ellen F

    2011-06-01

    Mitochondria in motor nerve terminals temporarily sequester large Ca(2+) loads during repetitive stimulation. In wild-type mice this Ca(2+) uptake produces a small (<5 mV), transient depolarization of the mitochondrial membrane potential (Ψ(m), motor nerve stimulated at 100 Hz for 5s). We demonstrate that this stimulation-induced Ψ(m) depolarization attains much higher amplitudes in motor terminals of symptomatic mice expressing the G93A or G85R mutation of human superoxide dismutase 1 (SOD1), models of familial amyotrophic lateral sclerosis (fALS). These large Ψ(m) depolarizations decayed slowly and incremented with successive stimulus trains. Additional Ψ(m) depolarizations occurred that were not synchronized with stimulation. These large Ψ(m) depolarizations were reduced (a) by cyclosporin A (CsA, 1-2 μM), which inhibits opening of the mitochondrial permeability transition pore (mPTP), or (b) by replacing bath Ca(2+) with Sr(2+), which enters motor terminals and mitochondria but does not support mPTP opening. These results are consistent with the hypothesis that the large Ψ(m) depolarizations evoked by repetitive stimulation in motor terminals of symptomatic fALS mice result from mitochondrial dysfunction that increases the likelihood of transient mPTP opening during Ca(2+) influx. Such mPTP openings, a sign of mitochondrial stress, would disrupt motor terminal handling of Ca(2+) loads and might thereby contribute to motor terminal degeneration in fALS mice. Ψ(m) depolarizations resembling those in symptomatic fALS mice could be elicited in wild-type mice following a 0.5-1h exposure to diamide (200 μM), which produces an oxidative stress, but these depolarizations were not reduced by CsA. PMID:21310237

  18. Sodium channels in presynaptic nerve terminals. Regulation by neurotoxins

    PubMed Central

    1980-01-01

    Regulation of Na+ channels by neurotoxins has been studied in pinched- off nerve endings (synaptosomes) from rat brain. Activation of Na+ channels by the steroid batrachotoxin and by the alkaloid veratridine resulted in an increase in the rate of influx of 22Na into the synaptosomes. In the presence of 145 mM Na+, these agents also depolarized the synaptosomes, as indicated by increased fluorescence in the presence of a voltage-sensitive oxacarbocyanine dye [diO-C5(3)]. Polypeptide neurotoxins from the scorpion Leiurus quinquestriatus and from the sea anemone Anthopleura xanthogrammica potentiated the stimulatory effects of batrachotoxin and veratridine on the influx of 22Na into synaptosomes. Saxitoxin and tetrodotoxin blocked the stimulatory effects of batrachotoxin and veratridine, both in the presence and absence of the polypeptide toxins, but did not affect control 22Na influx or resting membrane potential. A three-state model for Na+ channel operation can account for the effects of these neurotoxins on Na+ channels as determined both by Na+ flux measurements in vitro and by electrophysiological experiments in intact nerve and muscle. PMID:6252277

  19. Macrophage depletion lowers blood pressure and restores sympathetic nerve α2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats.

    PubMed

    Thang, Loc V; Demel, Stacie L; Crawford, Robert; Kaminski, Norbert E; Swain, Greg M; Van Rooijen, Nico; Galligan, James J

    2015-10-01

    We tested the hypothesis that vascular macrophage infiltration and O2 (-) release impairs sympathetic nerve α2-adrenergic autoreceptor (α2AR) function in mesenteric arteries (MAs) of DOCA-salt hypertensive rats. Male rats were uninephrectomized or sham operated (sham). DOCA pellets were implanted subcutaneously in uninephrectomized rats who were provided high-salt drinking water or high-salt water with apocynin. Sham rats received tap water. Blood pressure was measured using radiotelemetry. Treatment of sham and DOCA-salt rats with liposome-encapsulated clodronate was used to deplete macrophages. After 3-5, 10-13, and 18-21 days of DOCA-salt treatment, MAs and peritoneal fluid were harvested from euthanized rats. Norepinephrine (NE) release from periarterial sympathetic nerves was measured in vitro using amperometry with microelectrodes. Macrophage infiltration into MAs as well as TNF-α and p22(phox) were measured using immunohistochemistry. Peritoneal macrophage activation was measured by flow cytometry. O2 (-) was measured using dihydroethidium staining. Hypertension developed over 28 days, and apocynin reduced blood pressure on days 18-21. O2 (-) and macrophage infiltration were greater in DOCA-salt MAs compared with sham MAs after day 10. Peritoneal macrophage activation occurred after day 10 in DOCA-salt rats. Macrophages expressing TNF-α and p22(phox) were localized near sympathetic nerves. Impaired α2AR function and increased NE release from sympathetic nerves occurred in MAs from DOCA-salt rats after day 18. Macrophage depletion reduced blood pressure and vascular O2 (-) while restoring α2AR function in DOCA-salt rats. Macrophage infiltration into the vascular adventitia contributes to increased blood pressure in DOCA-salt rats by releasing O2 (-), which disrupts α2AR function, causing enhanced NE release from sympathetic nerves.

  20. Purinergic nerves and receptors.

    PubMed

    Burnstock, G

    1980-01-01

    The presence of a non-cholinergic, non-adrenergic component in the vertebrate autonomic nervous system is now well established. Evidence that ATP is the transmitter released from some of these nerves (called "purinergic') includes: (a) synthesis and storage of ATP in nerves: (b) release of ATP from the nerves when they are stimulated; (c) exogenously applied ATP mimicking the action of nerve-released transmitter; (d) the presence of ectoenzymes which inactivate ATP; (e) drugs which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. A basis for distinguishing two types of purinergic receptors has been proposed according to four criteria: relative potencies of agonists, competitive antagonists, changes in levels of cAMP and induction of prostaglandin synthesis. Thus P1 purinoceptors are most sensitive to adenosine, are competitively blocked by methylxanthines and their occupation leads to changes in cAMP accumulation; while P2 purinoceptors are most sensitive to ATP, are blocked (although not competitively) by quinidine, 2-substituted imidazolines, 2,2'-pyridylisatogen and apamin, and their occupation leads to production of prostaglandin. P2 purinoceptors mediate responses of smooth muscle to ATP released from purinergic nerves, while P1 purinoceptors mediate the presynaptic actions of adenosine on adrenergic, cholinergic and purinergic nerve terminals. PMID:6108568

  1. Motor nerve terminals on abdominal muscles in larval flesh flies, Sarcophaga bullata: comparisons with Drosophila.

    PubMed

    Feeney, C J; Karunanithi, S; Pearce, J; Govind, C K; Atwood, H L

    1998-12-14

    Motor nerve terminals on abdominal body-wall muscles 6A and 7A in larval flesh flies were investigated to establish their general structural features with confocal microscopy, transmission electron microscopy, and freeze-fracture procedures. As in Drosophila and other dipterans, two motor axons supply these muscles, and two morphologically different terminals were discerned with confocal microscopy: thin terminals with relatively small varicosities (Type Is), and thicker terminals with larger varicosities (Type Ib). In serial electron micrographs, Type Ib terminals were distinguished from Type Is terminals by their larger cross-sectional area, more extensive subsynaptic reticulum, more mitochondrial profiles, and more clear synaptic vesicles. Type Ib terminals possessed larger synapses and more synaptic contact area per unit terminal length. Although presynaptic dense bars of active zones were similar in mean length for the two terminal types, there were almost twice as many dense bars per synapse for Type Ib terminals. Freeze-fractures through the presynaptic membrane showed particle-free areas indicative of synapses on the P-face, within which were localized aggregations of large intramembranous particles indicative of active zones. These particles were similar in number to those found at active zones of several other arthropod neuromuscular junctions. In general, synaptic structural parameters strongly paralleled those of the anatomically homologous muscles in Drosophila melanogaster. In live preparations, simultaneous focal recording from identified varicosities and intracellular recording indicated that the two terminals produced excitatory junction potentials of similar amplitude in a physiological solution similar to that used for Drosophila.

  2. On the adrenergic system of ganoid fish: the beluga, Huso huso (chondrostei).

    PubMed

    Balashov, N V; Fänge, R; Govyrin, V A; Leont'eva, G R; Nilsson, S; Prozorovskaya, M P

    1981-04-01

    The adrenergic system of the beluga, Huso huso, was studied by glyoxylic acid fluorescence histochemistry, analyses of catecholamine content in various organs and studies of the effects of acetylcholine and adrenaline on isolated strip preparations from blood vessels, spleen, atrium and ventricle. Chromaffin cells were found mainly in the walls of the posterior cardinal veins, and to some extent also in the wall of the celiaco-mesenteric artery. The plasma concentration of adrenaline was high enough to affect the contraction force of the isolated atrial and ventricular strips, thus adding an adrenergic component to a possible cholinergic inhibitory vagal control of the heart. Fluorescence histochemistry revealed no direct adrenergic innervation of the heart, but blood vessels in the heart and elsewhere received a rich supply of adrenergic nerve terminals. Adrenaline contracted the celiaco-mesenteric artery and the spleen, and produced positive inotropic effects on the paced atrial and ventricular strip preparations. Acetylcholine contracted the ventral aorta and the celiaco-mesenteric artery, and reduced the contraction force of paced ventricular and, especially, atrial preparations. It is concluded that the beluga has a well developed adrenergic system consisting of both chromaffin cells and adrenergic neurons with varicose nerve terminals of the type found in the higher vertebrates. PMID:7304205

  3. Sympathetic nerve activity in normal and cystic follicles from isolated bovine ovary: local effect of beta-adrenergic stimulation on steroid secretion

    PubMed Central

    2011-01-01

    Cystic ovarian disease (COD) is an important cause of abnormal estrous behavior and infertility in dairy cows. COD is mainly observed in high-yielding dairy cows during the first months post-partum, a period of high stress. We have previously reported that, in lower mammals, stress induces a cystic condition similar to the polycystic ovary syndrome in humans and that stress is a definitive component in the human pathology. To know if COD in cows is also associated with high sympathetic activity, we studied isolated small antral (5mm), preovulatory (10mm) and cystic follicles (25mm). Cystic follicles which present an area 600 fold greater compared with preovulatory follicles has only 10 times less concentration of NE as compared with small antral and preovulatory follicles but they had 10 times more NE in follicular fluid, suggesting a high efflux of neurotransmitter from the cyst wall. This suggestion was reinforced by the high basal release of recently taken-up 3H-NE found in cystic follicles. While lower levels of beta-adrenergic receptor were found in cystic follicles, there was a heightened response to the beta-adrenergic agonist isoproterenol and to hCG, as measured by testosterone secretion. There was however an unexpected capacity of the ovary in vitro to produce cortisol and to secrete it in response to hCG but not to isoproterenol. These data suggest that, during COD, the bovine ovary is under high sympathetic nerve activity that in addition to an increased response to hCG in cortisol secretion could participate in COD development. PMID:21575217

  4. Control and Plasticity of the Presynaptic Action Potential Waveform at Small CNS Nerve Terminals

    PubMed Central

    Hoppa, Michael B.; Gouzer, Geraldine; Armbruster, Moritz; Ryan, Timothy A.

    2014-01-01

    SUMMARY The steep dependence of exocytosis on Ca2+ entry at nerve terminals implies that voltage control of both Ca2+ channel opening and the driving force for Ca2+ entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K+ channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property additionally shows adaptive plasticity: manipulations that increase presynaptic Ca2+ channel abundance and release probability result in a commensurate lowering of the APSYN peak and narrowing of the waveform, while manipulations that decrease presynaptic Ca2+ channel abundance do the opposite. This modulation is eliminated upon blockade of Kv3.1 and Kv1 channels. Our studies thus reveal that adaptive plasticity in the APSYN waveform serves as an important regulator of synaptic function. PMID:25447742

  5. Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive nerve terminals

    PubMed Central

    Sams-Nielsen, Anette; Orskov, Cathrine; Jansen-Olesen, Inger

    2001-01-01

    Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g. serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptide transmitters have not previously been reported. In the present study we present evidence for uptake of the 37 amino acid neuropeptide, calcitonin gene-related peptide (CGRP) into perivascular terminals of capsaicin sensitive nerve fibres, innervating the guinea-pig basilar artery. Release of CGRP from perivascular nerve terminals was obtained by capsaicin-induced vanilloid receptor-stimulation and detected as CGRP receptor-mediated dilation of isolated segments of the guinea-pig basilar artery. Following three repeated capsaicin challenges, CGRP-depleted segments were incubated with CGRP. This caused significant reappearance of capsaicin-induced vasodilatory responses. These responses were dependent on duration and concentration of the preceding CGRP incubation and were inhibited by the CGRP receptor antagonist, CGRP8–37. The CGRP-re-depletion was significantly reduced when CGRP8–37 was present during the preceding CGRP incubation. Thus, presynaptic CGRP receptors are likely to be involved in neuronal CGRP uptake. Incubating the artery segments with 125I-CGRP allowed subsequent detection of capsaicin-induced 125I-release. Immunohistochemical experiments showed that only terminal CGRP is subject to capsaicin-induced depletion in vitro, whereas CGRP-immunoreactivity endures in the nerve fibres. PMID:11226146

  6. Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.

    PubMed

    Kovács, Illés; Dienes, Lóránt; Perényi, Kristóf; Quirce, Susana; Luna, Carolina; Mizerska, Kamila; Acosta, M Carmen; Belmonte, Carlos; Gallar, Juana

    2016-09-15

    Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; P<0.05) and cold response (21.2±1.7 vs. 16.8±1.3imp/s; P<0.05) as well as reduced cold threshold (1.5±0.1 vs. 2.8±0.2 Δ°C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease. PMID:27263827

  7. cap alpha. -2 adrenergic receptor: a radiohistochemical study

    SciTech Connect

    Unnerstall, J.R.

    1984-01-01

    ..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the thoracic spinal cord. The transport of putative presynaptic ..cap alpha..-2 binding sites in the rat sciatic nerve was analyzed by light microscopic radiohistochemical techniques. Finally, in intact tissue section of the rat central nervous system, the biochemical characteristics of (/sup 3/H)rauwolscine binding were analyzed. Data were also shown which indicates that the synthetic ..cap alpha..-2 antagonist (/sup 3/H)RX781094 also binds to ..cap alpha..-2 receptors with high-affinity. Further, the distribution of (/sup 3/H)RX781094 binding sites in the rat central nervous system was identical to the distribution seen when using (/sup 3/H)para-aminoclonidine.

  8. Light microscopic image analysis system to quantify immunoreactive terminal area apposed to nerve cells

    NASA Technical Reports Server (NTRS)

    Wu, L. C.; D'Amelio, F.; Fox, R. A.; Polyakov, I.; Daunton, N. G.

    1997-01-01

    The present report describes a desktop computer-based method for the quantitative assessment of the area occupied by immunoreactive terminals in close apposition to nerve cells in relation to the perimeter of the cell soma. This method is based on Fast Fourier Transform (FFT) routines incorporated in NIH-Image public domain software. Pyramidal cells of layer V of the somatosensory cortex outlined by GABA immunolabeled terminals were chosen for our analysis. A Leitz Diaplan light microscope was employed for the visualization of the sections. A Sierra Scientific Model 4030 CCD camera was used to capture the images into a Macintosh Centris 650 computer. After preprocessing, filtering was performed on the power spectrum in the frequency domain produced by the FFT operation. An inverse FFT with filter procedure was employed to restore the images to the spatial domain. Pasting of the original image to the transformed one using a Boolean logic operation called 'AND'ing produced an image with the terminals enhanced. This procedure allowed the creation of a binary image using a well-defined threshold of 128. Thus, the terminal area appears in black against a white background. This methodology provides an objective means of measurement of area by counting the total number of pixels occupied by immunoreactive terminals in light microscopic sections in which the difficulties of labeling intensity, size, shape and numerical density of terminals are avoided.

  9. Modulation of presynaptic Ca(2+) currents in frog motor nerve terminals by high pressure.

    PubMed

    Aviner, Ben; Gradwohl, Gideon; Moore, Homer J; Grossman, Yoram

    2013-09-01

    Presynaptic Ca(2+) -dependent mechanisms have already been implicated in depression of evoked synaptic transmission by high pressure (HP). Therefore, pressure effects on terminal Ca(2+) currents were studied in Rana pipiens peripheral motor nerves. The terminal currents, evoked by nerve or direct stimulation, were recorded under the nerve perineurial sheath with a loose macropatch clamp technique. The combined use of Na(+) and K(+) channel blockers, [Ca(2+) ]o changes, voltage-dependent Ca(2+) channel (VDCC) blocker treatments and HP perturbations revealed two components of presynaptic Ca(2+) currents: an early fast Ca(2+) current (ICaF ), possibly carried by N-type (CaV 2.2) Ca(2+) channels, and a late slow Ca(2+) current (ICaS ), possibly mediated by L-type (CaV 1) Ca(2+) channels. HP reduced the amplitude and decreased the maximum (saturation level) of the Ca(2+) currents, ICaF being more sensitive to pressure, and may have slightly shifted the voltage dependence. HP also moderately diminished the Na(+) action current, which contributed to the depression of VDCC currents. Computer-based modeling was used to verify the interpretation of the currents and investigate the influence of HP on the presynaptic currents. The direct HP reduction of the VDCC currents and the indirect effect of the action potential decrease are probably the major cause of pressure depression of synaptic release. PMID:23738821

  10. Fangchinoline inhibits glutamate release from rat cerebral cortex nerve terminals (synaptosomes).

    PubMed

    Lin, Tzu-Yu; Lu, Cheng-Wei; Tien, Lu-Tai; Chuang, Shu-Han; Wang, Yu-Ru; Chang, Wen-Hsuan; Wang, Su-Jane

    2009-07-01

    Fangchinoline, an active component of radix stephaniae tetrandrinea, has been shown to possess neuroprotective properties. It has been reported that excessive glutamate release has been proposed to be involved in the pathogenesis of several neurological diseases. The primary purpose of the present study was to investigate the effect of fangchinoline on glutamate release in rat cerebral cortex nerve terminals and to explore the possible mechanism. Fangchinoline inhibited the release of glutamate evoked by 4-aminopyridine (4-AP) in a concentration-dependent manner, and this phenomenon resulted from a reduction of vesicular exocytosis but not from an inhibition of Ca(2+)-independent efflux via glutamate transporter. Fangchinoline did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization, but significantly reduced depolarization-induced increase in [Ca(2+)](C). Fangchinoline-mediated inhibition of glutamate release was significantly prevented by the N- and P/Q-type Ca(2+) channel blocker omega-conotoxin MVIIC, and by the PKC inhibitors, GF109203X and Ro318220. In addition, the glutamate release mediated by direct Ca(2+) entry with Ca(2+) ionophore (ionomycin) was unaffected by fangchinoline, which suggests that the inhibitory effect of fangchinoline is not due to directly interfering with the release process at some point subsequent to Ca(2+) influx. These results suggest that fangchinoline inhibits glutamate release from the rat cortical synaptosomes through the suppression of voltage-dependent Ca(2+) channel activity and subsequent reduces Ca(2+) entry into nerve terminals, rather than any upstream effect on nerve terminal excitability. This inhibition appears to involve the suppression of PKC signal transduction pathway. This finding may explain the neuroprotective effects of fangchinoline against neurotoxicity. PMID:19428795

  11. Phosphatidylinositol 3-Kinase Couples Localised Calcium Influx to Activation of Akt in Central Nerve Terminals.

    PubMed

    Nicholson-Fish, Jessica C; Cousin, Michael A; Smillie, Karen J

    2016-03-01

    The efficient retrieval of synaptic vesicle membrane and cargo in central nerve terminals is dependent on the efficient recruitment of a series of endocytosis modes by different patterns of neuronal activity. During intense neuronal activity the dominant endocytosis mode is activity-dependent endocytosis (ADBE). Triggering of ADBE is linked to calcineurin-mediated dynamin I dephosphorylation since the same stimulation intensities trigger both. Dynamin I dephosphorylation is maximised by a simultaneous inhibition of its kinase glycogen synthase kinase 3 (GSK3) by the protein kinase Akt, however it is unknown how increased neuronal activity is transduced into Akt activation. To address this question we determined how the activity-dependent increases in intracellular free calcium ([Ca(2+)]i) control activation of Akt. This was achieved using either trains of high frequency action potentials to evoke localised [Ca(2+)]i increases at active zones, or a calcium ionophore to raise [Ca(2+)]i uniformly across the nerve terminal. Through the use of either non-specific calcium channel antagonists or intracellular calcium chelators we found that Akt phosphorylation (and subsequent GSK3 phosphorylation) was dependent on localised [Ca(2+)]i increases at the active zone. In an attempt to determine mechanism, we antagonised either phosphatidylinositol 3-kinase (PI3K) or calmodulin. Activity-dependent phosphorylation of both Akt and GSK3 was arrested on inhibition of PI3K, but not calmodulin. Thus localised calcium influx in central nerve terminals activates PI3K via an unknown calcium sensor to trigger the activity-dependent phosphorylation of Akt and GSK3.

  12. Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

    PubMed

    Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

    2016-01-28

    In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain.

  13. Membrane depolarization and carbamoylcholine stimulate phosphatidylinositol turnover in intact nerve terminals

    SciTech Connect

    Audigier, S.M.P.; Wang, J.K.T.; Greengard, P.

    1988-04-01

    Synaptosomes, purified from rat cerebral cortex, were prelabeled with (/sup 3/H)inositol to study phosphatidylinositol turnover in nerve terminals. Labeled synaptosomes were either depolarized with 40 mM K/sup +/ or exposed to carbamoylcholine (carbachol). K/sup +/ depolarization increased the level of inositol phosphates in a time-dependent manner. The inositol bisphosphate level also increased rapidly, but its elevated level was sustained during continued depolarization. The elevated level of inositol bisphosphate was reversed upon repolarization of the synaptosomes. The level of inositol monophosphate increased slowly to 120-130% of control. These effects of K/sup +/ depolarization depended on the presence of Ca/sup 2 +/ in the incubation medium. Carbachol stimulated the turnover of phosphatidylinositol in a dose- and time-dependent manner. The level of inositol bisphosphate increased to 210% of control, and this maximal response was seen from 15 to 60 min. Accumulation of inositol monophosphate was larger than that of inositol bisphosphate, but its time course was slower. Atropine and pirenzepine inhibited the carbachol effect with high affinities. These data show that both Ca/sup 2 +/ influx and M/sub 1/ muscarinic receptor activation stimulate phospholipase C activity in synaptosomes, suggesting that phosphatidylinositol turnover may be involved in regulating neurotransmitter release from nerve terminals.

  14. The effects of dietary protein restriction on chorda tympani nerve taste responses and terminal field organization.

    PubMed

    Thomas, J E; Hill, D L

    2008-11-19

    Prenatal dietary sodium restriction produces profound developmental effects on rat functional taste responses and formation of neural circuits in the brainstem. Converging evidence indicates that the underlying mechanisms for these effects are related to a compromised nutritional state and not to direct stimulus-receptor interactions. We explored whether early malnourishment produces similar functional and structural effects to those seen following dietary sodium restriction by using a protein deficient, sodium replete diet. To determine if early dietary protein-restriction affects the development of the peripheral gustatory system, multi-fiber neurophysiological recordings were made from the chorda tympani nerve and anterograde track tracing of the chorda tympani nerve into the nucleus of the solitary tract (NTS) was accomplished in rats fed a protein-restricted or a control diet (6% and 20%, respectively). The dietary regimens began on embryonic day 7 and continued until rats were used for neurophysiological recordings (postnatal days (P) 35-50) or for chorda tympani terminal field labeling (P40-50). Responses to a concentration series of NaCl, sodium acetate, KCl, and to 0.50 M sucrose, 0.03 M quinine-HCl, and 0.01 N HCl revealed attenuated responses (30-60%) to sodium-specific stimuli in rats fed the 6% protein diet compared with those fed the 20% protein diet. Responses to all other stimuli were similar between groups. Terminal field volumes were nearly twofold larger in protein-restricted rats compared with controls, with the differences located primarily in the dorsal-caudal zone of the terminal field. These results are similar to the results seen previously in rats fed a sodium-restricted diet throughout pre- and postnatal development, suggesting that dietary sodium- and protein-restriction share similar mechanisms in altering gustatory development.

  15. THE EFFECT OF NITRIC OXIDE ON SYNAPTIC VESICLE PROTON GRADIENT AND MITOCHONDRIAL POTENTIAL OF BRAIN NERVE TERMINALS.

    PubMed

    Tarasenko, A S

    2015-01-01

    The effect of nitric oxide on synaptic vesicle proton gradient and membrane potential of rat brain nerve terminals was studied. It has been shown that nitric oxide in the form of S-nitrosothiols at nanomolar concentrations had no effect on the studied parameters, but caused a rapid dissipation of synaptic vesicle proton gradient and depolarization of mitochondrial membrane in the presence of a SH-reducing compound such as dithiothreitol. Both processes were reversible and the rate of H(+)-gradient restoration depended on the redox potential of nerve terminals, namely the molar ratio of reductant/oxidant. This facts, as well as insensitivity of the studied processes to the inhibitor of NO-sensitive guanylate cyclase such as ODQ, allow suggesting that post-translational modification of thiol residues of the mitochondrial and synaptic vesicle proteins underlies the effect of nitric oxide on the key functional parameters ofpresynaptic nerve terminals. PMID:27025060

  16. Early prenatal critical period for chorda tympani nerve terminal field development.

    PubMed

    Krimm, R F; Hill, D L

    1997-02-10

    In order to determine whether the developing central gustatory system responds to dietary manipulation during restricted developmental periods, terminal fields of the chorda tympani nerve within the nucleus of the solitary tract were investigated via anterograde transport of horseradish peroxidase in control rats and in rats in which a low sodium diet was systematically fed during specific periods of development. Rats fed a low sodium diet (0.03% NaCl) from embryonic day 3 (E3) to day E12 and then fed a sodium replete diet to at least 60 days postnatal exhibited enlarged and irregularly shaped chorda tympani terminal fields. Specifically, the dorsal zone of the field was the smallest in controls, whereas it was the largest in restricted rats, occupying more territory within the nucleus. This alteration in the terminal field was apparent in all groups of rats fed the low-NaCl diet beginning at E3, and continuing beyond E12. In contrast, no effects of the dietary manipulation on the developing chorda tympani field was evident when it occurred from E3 to day E9, from E0 to day E9 or when it occurred at adulthood only. Therefore, only 9 days of maternal exposure to a sodium-restricted diet is required for a permanent expansion of the chorda tympani terminal field in the offspring. Moreover, a brief period from E9 to E12 must be included within the 9-day dietary restriction to yield the expanded field. Since this period is before taste receptors appear on the tongue, it is likely that nonactivity-dependent factors determine the formation of the chorda tympani terminal field during later development.

  17. “Late” Macroendosomes and Acidic Endosomes in Vertebrate Motor Nerve Terminals

    PubMed Central

    Stewart, Richard S.; Teng, Haibing; Wilkinson, Robert S.

    2014-01-01

    Activity at the vertebrate nerve—muscle synapse creates large macroendosomes (MEs) via bulk membrane infolding. Visualized with the endocytic probe FM1-43, most (94%) of the ~25 MEs/terminal created by brief (30-Hz, 18-second) stimulation dissipate rapidly (~1 minute) into vesicles. Others, however, remain for hours. Here we study these “ late” MEs by using 4D live imaging over a period of ~1 hour after stimulation. We find that some (51/398 or 13%) disappear spontaneously via exocytosis, releasing their contents into the extracellular milieu. Others (at least 15/1,960 or 1%) fuse or closely associate with a second class of endosomes that take up acidophilic dyes (acidic endosomes [AEs]). AEs are plentiful (~47/terminal) and exist independent of stimulation. Unlike MEs, which exhibit Brownian motion, AEs exhibit directed motion (average, 83 nm/sec) on microtubules within and among terminal boutons. AEs populate the axon as well, where movement is predominantly retrograde. They share biochemical and immunohistochemical markers (e.g., lysosomal-associated membrane protein [LAMP-1]) with lysosomes. Fusion/association of MEs with AEs suggests a sorting/degradation pathway in nerve terminals wherein the role of AEs is similar to that of lysosomes. Based on our data, we propose that MEs serve as sorting endosomes. Thus their contents, which include plasma membrane proteins, vesicle proteins, and extracellular levels of Ca2+, can be targeted either toward the reformation and budding of synaptic vesicles, toward secretion via exocytosis, or toward a degradation process that utilizes AEs either for lysis within the terminal or for transport toward the cell body. PMID:22740045

  18. Lunar and Martian soil stimulants have different effects on L-[14C]glutamate binding to brain nerve terminals

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Nazarova, Anastasiya; Borysov, Arseniy; Chunihin, Olexander

    Nano-sized particles can be deleterious to human physiology because they may be internalized by lung epithelium and overcome the blood-brain barrier. The health effects from exposure to Lunar and Martian dust are almost completely unknown, whereas they can be deleterious to human physiology. The effects of Lunar and Martian Soil Simulants (Orbital Technologies Corporation, Madison, USA) on the conductance of planar lipid membrane, membrane potential, acidification of synaptic vesicles, glutamate uptake, and ambient level of glutamate in isolated rat brain nerve terminals (synaptosomes) were studied using photon correlation spectroscopy, Planar Lipid Bilayer technique, spectrofluorimetry, radiolabeled assay, respectively. Lunar and Martian Soil Simulants did not influence the conductance of planar lipid membrane. It was revealed that nerve terminals were not indifferent to the exposure to inorganic particles of Lunar and Martian Soil Simulants. Using Zetasizer Nanosystem (Malvern Instruments) with helium-neon laser for dynamic light scattering (DLS), the synaptosomal size before and after the addition of Lunar and Martian Soil Simulants was measured and the binding of Lunar and Martian Soil Simulants inorganic particles to nerve terminals was demonstrated. Using potential-sensitive fluorescent dye rhodamine 6G, we showed that Lunar and Martian Soil particles did not influence the potential of the plasma membrane of nerve terminals. Acidification of synaptic vesicles of nerve terminals was not changed in the presence of Lunar and Martian Soil particles that was revealed with pH-sensitive fluorescent dye acridine orange. Martian Soil Simulant particles did not change binding of L-[14C]glutamate to brain nerve terminals, in contrast, Lunar ones changed this parameter and this fact may have harmful consequences to human physiology, in particular, glutamate homeostasis in the mammalian CNS.

  19. Interaction of /sup 125/I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis

    SciTech Connect

    Black, J.D.; Dolly, J.O.

    1986-01-01

    Using pharmacological and autoradiographic techniques it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In the present study, the nature of this uptake process was investigated using electron microscopic autoradiography. It was found that internalization is acceptor-mediated and that binding to specific cell surface acceptors involves the heavier chain of the toxin. In addition, uptake was shown to be energy and temperature-dependent and to be accelerated by nerve stimulation, a treatment which also shortens the time course of the toxin-induced neuroparalysis. These results, together with the observation that silver grains were often associated with endocytic structures within the nerve terminal, suggested that acceptor-mediated endocytosis is responsible for toxin uptake. Possible recycling of BoNT acceptors (an important aspect of acceptor-mediated endocytosis of toxins) at motor nerve terminals was indicated by comparing the extent of labeling in the presence and absence of metabolic inhibitors. On the basis of these collective results, it is concluded that BoNT is internalized by acceptor-mediated endocytosis and, hence, the data support the proposal that this toxin inhibits release of acetylcholine by interaction with an intracellular target.

  20. Live imaging of bulk endocytosis in frog motor nerve terminals using FM dyes

    PubMed Central

    Gaffield, Michael A.; Romberg, Christin F.

    2011-01-01

    We observed endocytosis in real time in stimulated frog motor nerve terminals by imaging the growth of large membrane infoldings labeled with a low concentration of FM dye. The spatial and temporal information made available by these experiments allowed us to image several new aspects of this synaptic vesicle recycling pathway. Membrane infoldings appeared near synaptic vesicle clusters and grew rapidly during long-duration, high-frequency stimulation. In some cases, we observed large, elongated infoldings growing laterally into the terminal. We used these observations to calculate infolding growth rates. A decrease in stimulation frequency caused a decrease in growth rates, but the overall length of these structures was unaffected by frequency changes. Attempts to wash the dye from these infoldings after stimulation were unsuccessful, demonstrating that the fluorescent structures had been endocytosed. We also used this technique to trigger and image infoldings during repeated, short trains. We found that membrane uptake occurred repeatedly at individual endocytosis sites, but only during a portion of the total number of trains delivered to the terminal. Finally, we showed that phosphatidylinositol 3-kinase, but not actin, was involved in this endocytosis pathway. The ability to monitor many individual bulk endocytosis sites in real time should allow for new types of endocytosis measurements and could reveal novel and unexpected mechanisms for coordinating membrane recovery during synaptic activity. PMID:21543750

  1. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  2. Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex.

    PubMed

    Su, Jianmin; Chen, Jiang; Lippold, Kumiko; Monavarfeshani, Aboozar; Carrillo, Gabriela Lizana; Jenkins, Rachel; Fox, Michael A

    2016-03-14

    Inhibitory synapses comprise only ∼20% of the total synapses in the mammalian brain but play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia and epilepsy. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Here, we discovered a novel role for an unconventional collagen-collagen XIX-in the formation of Parvalbumin(+) inhibitory synapses. Loss of this collagen results not only in decreased inhibitory synapse number, but also in the acquisition of schizophrenia-related behaviors. Mechanistically, these studies reveal that a proteolytically released fragment of this collagen, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. Collectively, these studies not only identify roles for collagen-derived matricryptins in cortical circuit formation, but they also reveal a novel paracrine mechanism that regulates the assembly of these synapses.

  3. Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

    PubMed Central

    Su, Jianmin; Chen, Jiang; Lippold, Kumiko; Monavarfeshani, Aboozar; Carrillo, Gabriela Lizana; Jenkins, Rachel

    2016-01-01

    Inhibitory synapses comprise only ∼20% of the total synapses in the mammalian brain but play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia and epilepsy. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Here, we discovered a novel role for an unconventional collagen—collagen XIX—in the formation of Parvalbumin+ inhibitory synapses. Loss of this collagen results not only in decreased inhibitory synapse number, but also in the acquisition of schizophrenia-related behaviors. Mechanistically, these studies reveal that a proteolytically released fragment of this collagen, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. Collectively, these studies not only identify roles for collagen-derived matricryptins in cortical circuit formation, but they also reveal a novel paracrine mechanism that regulates the assembly of these synapses. PMID:26975851

  4. Allopregnanolone modulates spontaneous GABA release via presynaptic Cl- permeability in rat preoptic nerve terminals.

    PubMed

    Haage, David; Druzin, Michael; Johansson, Staffan

    2002-12-27

    The endogenous neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) affects presynaptic nerve terminals and thereby increases the frequency of spontaneous GABA release. The present study aimed at clarifying the mechanisms underlying this presynaptic neurosteroid action, by recording the frequency of spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in neurons from the medial preoptic nucleus (MPN) of rat. Acutely dissociated neurons with functional adhering nerve terminals were studied by perforated-patch recording under voltage-clamp conditions. It was shown that the sIPSC frequency increased with the external K(+) concentration ([K(+)](o)). Further, the effect of allopregnanolone on the sIPSC frequency was strongly dependent on [K(+)](o). In a [K(+)](o) of 5 mM, 2.0 microM allopregnanolone caused a clear increase in sIPSC frequency. However, the effect declined rapidly with increased [K(+)](o) and at high [K(+)](o) allopregnanolone reduced the sIPSC frequency. The effect of allopregnanolone was also strongly dependent on the external Cl(-) concentration ([Cl(-)](o)). In a reduced [Cl(-)](o) (40 mM, but with a standard [K(+)](o) of 5 mM), the effect on sIPSC frequency was larger than that in the standard [Cl(-)](o) of 146 mM. The dependence of the effect of allopregnanolone on [K(+)](o) and on estimated presynaptic membrane potential was also altered by the reduction in [Cl(-)](o). As in standard [Cl(-)](o), the effect in low [Cl(-)](o) declined when [K(+)](o) was raised, but reversed at a higher [K(+)](o). The GABA(A) receptor agonist muscimol also potentiated the sIPSC frequency. Altogether, the results suggest that allopregnanolone exerts its presynaptic effect by increasing the presynaptic Cl(-) permeability, most likely via GABA(A) receptors. PMID:12470877

  5. Visualization of endosome dynamics in living nerve terminals with four-dimensional fluorescence imaging.

    PubMed

    Stewart, Richard S; Kiss, Ilona M; Wilkinson, Robert S

    2014-01-01

    Four-dimensional (4D) light imaging has been used to study behavior of small structures within motor nerve terminals of the thin transversus abdominis muscle of the garter snake. Raw data comprises time-lapse sequences of 3D z-stacks. Each stack contains 4-20 images acquired with epifluorescence optics at focal planes separated by 400-1,500 nm. Steps in the acquisition of image stacks, such as adjustment of focus, switching of excitation wavelengths, and operation of the digital camera, are automated as much as possible to maximize image rate and minimize tissue damage from light exposure. After acquisition, a set of image stacks is deconvolved to improve spatial resolution, converted to the desired 3D format, and used to create a 4D "movie" that is suitable for variety of computer-based analyses, depending upon the experimental data sought. One application is study of the dynamic behavior of two classes of endosomes found in nerve terminals-macroendosomes (MEs) and acidic endosomes (AEs)-whose sizes (200-800 nm for both types) are at or near the diffraction limit. Access to 3D information at each time point provides several advantages over conventional time-lapse imaging. In particular, size and velocity of movement of structures can be quantified over time without loss of sharp focus. Examples of data from 4D imaging reveal that MEs approach the plasma membrane and disappear, suggesting that they are exocytosed rather than simply moving vertically away from a single plane of focus. Also revealed is putative fusion of MEs and AEs, by visualization of overlap between the two dye-containing structures as viewed in each three orthogonal projections. PMID:24799002

  6. Quantal potential fields around individual active zones of amphibian motor-nerve terminals.

    PubMed Central

    Bennett, M R; Farnell, L; Gibson, W G; Macleod, G T; Dickens, P

    2000-01-01

    The release of a quantum from a nerve terminal is accompanied by the flow of extracellular current, which creates a field around the site of transmitter action. We provide a solution for the extent of this field for the case of a quantum released from a site on an amphibian motor-nerve terminal branch onto the receptor patch of a muscle fiber and compare this with measurements of the field using three extracellular electrodes. Numerical solution of the equations for the quantal potential field in cylindrical coordinates show that the density of the field at the peak of the quantal current gives rise to a peak extracellular potential, which declines approximately as the inverse of the distance from the source at distances greater than about 4 microm from the source along the length of the fiber. The peak extracellular potential declines to 20% of its initial value in a distance of about 6 microm, both along the length of the fiber and in the circumferential direction around the fiber. Simultaneous recordings of quantal potential fields, made with three electrodes placed in a line at right angles to an FM1-43 visualized branch, gave determinations of the field strengths in accord with the numerical solutions. In addition, the three electrodes were placed so as to straddle the visualized release sites of a branch. The positions of these sites were correctly predicted on the basis of the theory and independently ascertained by FM1-43 staining of the sites. It is concluded that quantal potential fields at the neuromuscular junction that can be measured with available recording techniques are restricted to regions within about 10 microm of the release site. PMID:10692301

  7. High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

    NASA Astrophysics Data System (ADS)

    Salzberg, Brian M.

    2008-03-01

    Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

  8. Study on distribution of terminal branches of the facial nerve in mimetic muscles (orbicularis oculi muscle and orbicularis oris muscle).

    PubMed

    Mitsukawa, Nobuyuki; Moriyama, Hiroshi; Shiozawa, Kei; Satoh, Kaneshige

    2014-01-01

    There have been many anatomical reports to date regarding the course of the facial nerve to the mimetic muscles. However, reports are relatively scarce on the detailed distribution of the terminal branches of the facial nerve to the mimetic muscles. In this study, we performed detailed examination of the terminal facial nerve branches to the mimetic muscles, particularly the branches terminating in the orbicularis oculi muscle and orbicularis oris muscle. Examination was performed on 25 Japanese adult autopsy cases, involving 25 hemifaces. The mean age was 87.4 years (range, 60-102 years). There were 12 men and 13 women (12 left hemifaces and 13 right hemifaces). In each case, the facial nerve was exposed through a preauricular skin incision. The main trunk of the facial nerve was dissected from the stylomastoid foramen. A microscope was used to dissect the terminal branches to the periphery and observe them. The course and distribution were examined for all terminal branches of the facial nerve. However, focus was placed on the course and distribution of the zygomatic branch, buccal branch, and mandibular branch to the orbicularis oculi muscle and orbicularis oris muscle. The temporal branch was distributed to the orbicularis oculi muscle in all cases and the marginal mandibular branch was distributed to the orbicularis oris muscle in all cases. The zygomatic branch was distributed to the orbicularis oculi muscle in all cases, but it was also distributed to the orbicularis oris muscle in 10 of 25 cases. The buccal branch was not distributed to the orbicularis oris muscle in 3 of 25 cases, and it was distributed to the orbicularis oculi muscle in 8 cases. There was no significant difference in the variations. The orbicularis oculi muscle and orbicularis oris muscle perform particularly important movements among the facial mimetic muscles. According to textbooks, the temporal branch and zygomatic branch innervate the orbicularis oculi muscle, and the buccal branch

  9. Release of calcitonin gene-related peptide from nerve terminals in rat skeletal muscle.

    PubMed Central

    Sakaguchi, M; Inaishi, Y; Kashihara, Y; Kuno, M

    1991-01-01

    1. The amount of calcitonin gene-related peptide (CGRP) released from the isolated rat soleus muscle was measured by enzyme immunoassay. 2. When the soleus muscle was exposed to a solution containing high K+ (20-100 mM) in the presence of tetrodotoxin, the amount of CGRP released into the bathing medium increased with an increase in the K+ concentration. 3. The exposure to 100 mM-K+ did not increase CGRP release from chronically denervated soleus muscles or from pieces of the soleus nerve separated from the muscle. 4. The amount of CGRP released from the isolated muscle by 100 mM-K+ depended on the external Ca2+ concentration. The slope of the relation between the amount of CGRP release and the Ca2+ concentration was less than one on double logarithmic co-ordinates. 5. Following chronic section of the lumbar ventral roots, the mean amount of CGRP released from the soleus muscle by 100 mM-K+ was reduced by 28%, compared with that observed in normal muscle. 6. Antidromic stimulation of the lumbar dorsal roots at an intensity three times the threshold for most excitable sensory fibres failed to induce CGRP release from the soleus muscle, whereas stimulation at intensities 50-100 times the threshold increased significantly the amount of CGRP release from the muscle. 7. Stimulation of the muscle nerve at an intensity sufficient to activate the alpha-motor fibres did not release CGRP from the soleus muscle or from the diaphragm. 8. It is concluded that the major source of CGRP released from skeletal muscle is A delta- and/or C sensory terminals and that the Ca2+ dependence of CGRP release is less steep than that reported for acetylcholine release at neuromuscular junctions. PMID:2023119

  10. Some properties of the presynaptic nerve terminals in a mammalian sympathetic ganglion

    PubMed Central

    Dunant, Y.

    1972-01-01

    1. Superior cervical ganglia of adult rats were excised and maintained in vitro in stable conditions. Potentials were recorded with external electrodes. After transmission was blocked by mecamylamine, a small potential change was recorded from the rostral area of the ganglion in response to preganglionic stimulation. 2. This electrical response was identified as the presynaptic action potential recorded from the nerve terminals by a number of criteria based on histological and physiological considerations including the disappearance of the spike in a glucose free solution. As shown by Nicolescu, Dolivo, Rouiller & Foroglou-Kerameus (1966) on the same preparation this condition causes an irreversible and selective lesion of the presynaptic nerve endings. 3. A suitable concentration of mecamylamine permitted the presynaptic response and the excitatory post-synaptic potential (EPSP) to be recorded simultaneously. As the stimulus was increased, the EPSP increased linearly with the amplitude of the presynaptic response. 4. After replacement of potassium ions in the bathing solution by caesium and during the early phase of post-tetanic facilitation there was an increase in the presynaptic response accompanied by a disproportionate increase in the EPSP. 5. No changes in the presynaptic response were found in the presence of the following drugs, all of which depressed the EPSP: acetylcholine, hemicholinium, curare, further doses of ganglion-blocking agents, and high Mg2+ and low Ca2+ concentrations. 6. Ouabain (4·5 × 10-4 M) reversibly decreased the amplitude of the presynaptic response and increased the spontaneous release of transmitter. The EPSP was at first enhanced and then depressed. PMID:4335802

  11. The role of calcium in depolarization-secretion coupling at the motor nerve terminal.

    PubMed

    Cooke, J D; Okamoto, K; Quastel, D M

    1973-01-01

    1. The relation between m.e.p.p. frequency (F) and [Ca] was studied at the mouse neuromuscular junction, at varied concentrations of K(+) and at nerve terminals depolarized by focal depolarization.2. Under all conditions the relation between log F and log [Ca] was sigmoid, with a maximum slope that increased with depolarization or raised [K(+)]. In addition, depolarization or raised K(+) caused a progressive shift of the sigmoid curve upward and to the left (to reduced log [Ca]) and increased the range over which log F could be altered by [Ca].3. Reduction of osmotic pressure changed the relation between log F and log [Ca] in the same way as increase of depolarization, while increase of osmotic pressure did the opposite.4. Raised [Mg] acted in two ways: (a) to shift the curve of log F vs. log [Ca] to the right and (b) to reduce maximum Delta log F/Delta log [Ca] without altering the range of log F sensitive to [Ca].5. The relation between log quantal content of e.p.p.s and log [Ca] was similar to that between log m.e.p.p. frequency and log [Ca].6. Individual nerve terminals varied in both Ca-dependent and Ca-independent fractions of log F; a large Ca-independent portion appears to be associated with a low Ca-dependent portion and vice versa. With large prolonged depolarization the Ca-independent portion was increased, apparently at the expense of the Ca-dependent portion.7. The results of all experiments were summarized in terms of parameters found by fitting the observed log release -log [Ca] curves to two theoretical equations, each derived on the basis of a model: (a) all-or-nothing activation of release probability by Ca-complex(es) and (b) graded activation of release probability by Ca complex(es).8. On the basis of the all-or-nothing model, from which follows alinear relation between F and amounts of Ca complex(es), the number of Ca(2+) atoms that ;cooperate' to mediate release appeared to increase progressively with presynaptic depolarization, to a value of

  12. Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals

    PubMed Central

    Tian, >Lijun; Prior, Chris; Dempster, John; Marshall, Ian G

    1997-01-01

    The neuronal nicotinic receptor antagonists hexamethonium and methyllycaconitine (MLA) have been used to study the putative prejunctional nicotinic ACh receptors (AChRs) mediating a negative-feedback control of ACh release from motor nerve terminals in voltage-clamped rat phrenic nerve/hemidiaphragm preparations. Hexamethonium (200 μM), but not MLA (0.4–2.0 μM), decreased the time constant of decay of both endplate currents (e.p.cs) and miniature endplate currents (m.e.p.cs), indicating endplate ion channel block with hexamethonium. However, driving function analysis and reconvolution of e.p.cs and m.e.p.cs indicated that this ion channel block did not compromise the analysis of e.p.c. quantal content. At low frequencies of stimulation (0.5–2 Hz), hexamethonium (200 μM) and MLA (2.0 μM) increased e.p.c. quantal content by 30–40%. At high frequencies (50–150 Hz) neither compound affected e.p.c. quantal content. All effects on quantal content were paralleled by changes in the size of the pool of quanta available for release. The low frequency augmentation of e.p.c. quantal content by hexamethonium was absent when extracellular [Ca2+] was lowered from 2.0 to 0.5 mM. At the concentrations studied, MLA and hexamethonium produced a small (10–20%) decrease in the peak amplitude of m.e.p.cs. Neither apamin (100 nM) nor charybdotoxin (80 nM) had effects on spontaneous or nerve evoked current amplitudes at any frequency of stimulation. Thus the ability of nicotinic antagonists to augment e.p.c. quantal content is not due to inhibition of Ca2+-activated K+-channels. We suggest that hexamethonium and MLA increase evoked ACh release by blocking prejunctional nicotinic AChRs. These receptors exert a negative feedback control over evoked ACh release and are probably of the α-bungarotoxin-insensitive neuronal type. PMID:9401765

  13. Berberine Inhibits the Release of Glutamate in Nerve Terminals from Rat Cerebral Cortex

    PubMed Central

    Lu, Cheng-Wei; Huang, Shu-Kuei; Wang, Su-Jane

    2013-01-01

    Berberine, an isoquinoline plant alkaloid, protects neurons against neurotoxicity. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study, we investigated whether berberine could affect endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes) and explored the possible mechanism. Berberine inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP), and this phenomenon was prevented by the chelating extracellular Ca2+ ions and the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Inhibition of glutamate release by berberine was not due to it decreasing synaptosomal excitability, because berberine did not alter 4-AP-mediated depolarization. The inhibitory effect of berberine on glutamate release was associated with a reduction in the depolarization-induced increase in cytosolic free Ca2+ concentration. Involvement of the Cav2.1 (P/Q-type) channels in the berberine action was confirmed by blockade of the berberine-mediated inhibition of glutamate release by the Cav2.1 (P/Q-type) channel blocker ω-agatoxin IVA. In addition, the inhibitory effect of berberine on evoked glutamate release was prevented by the mitogen-activated/extracellular signal-regulated kinase kinase (MEK) inhibitors. Berberine decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synapsin I, the main presynaptic target of ERK; this decrease was also blocked by the MEK inhibition. Moreover, the inhibitory effect of berberine on evoked glutamate release was prevented in nerve terminals from mice lacking synapsin I. Together, these results indicated that berberine inhibits glutamate release from rats cortical synaptosomes, through the suppression of presynaptic Cav2.1 channels and ERK/synapsin I signaling

  14. Altered Active Zones, Vesicle Pools, Nerve Terminal Conductivity, and Morphology during Experimental MuSK Myasthenia Gravis

    PubMed Central

    Patel, Vishwendra; Oh, Anne; Voit, Antanina; Sultatos, Lester G.; Babu, Gopal J.; Wilson, Brenda A.; Ho, Mengfei; McArdle, Joseph J.

    2014-01-01

    Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG. PMID:25438154

  15. Simulatory effect of porcine insulin on noradrenaline secretion in guinea-pig ileum myenteric nerve terminals

    PubMed Central

    Cheng, Juei-Tang; Hung, Chen-Road; Lin, Ming-I

    1997-01-01

    The effect of insulin on the release of noradrenaline (NA) from nerve terminals was investigated in isolated ileal synaptosomes of guinea-pig. Release was determined as the amount of NA, quantified by h.p.l.c.-electrochemical detection, from samples incubated with insulin minus that in parallel blanks treated with some volume of vehicle.Porcine insulin stimulated the secretion of NA in a concentration-dependent manner from 0.01 i.u. ml−1, while the value of lactate dehydrogenase in the incubated medium was not influenced by insulin.The presence of insulin receptors in this preparation was illustrated by immunoblotting with insulin receptor monoclonal antibodies.The release of NA by insulin was reduced by guanethidine and bretylium and it was markedly lowered in the samples obtained from guinea-pigs that had received an intraperitoneal injection of DSP-4, the noradrenergic neurotoxin.Tetrodotoxin attenuated the action of insulin at concentrations sufficient to block sodium channels. The depolarizing effect of insulin on the membrane potential was also illustrated by a concentration-dependent increase in the fluorescence of bisoxonol, a potential-sensitive dye.The action of insulin was attenuated by removal of calcium chloride from the bathing medium. The induction of calcium ion influx by insulin into the synaptosomes is supported by the inhibitory effects of the calcium channel blockers ω-conotoxin GVIA (for the N-type channels) and nifedipine (for the L-type channels).These findings suggest that insulin can stimulate NA release from noradrenergic terminals via activation of calcium influx. PMID:9146881

  16. Phosphorylation of septin 3 on Ser-91 by cGMP-dependent protein kinase-I in nerve terminals

    PubMed Central

    2004-01-01

    The septins are a family of GTPase enzymes required for cytokinesis and play a role in exocytosis. Among the ten vertebrate septins, Sept5 (CDCrel-1) and Sept3 (G-septin) are primarily concentrated in the brain, wherein Sept3 is a substrate for PKG-I (cGMP-dependent protein kinase-I) in nerve terminals. There are two motifs for potential PKG-I phosphorylation in Sept3, Thr-55 and Ser-91, but phosphoamino acid analysis revealed that the primary site is a serine. Derivatization of phosphoserine to S-propylcysteine followed by N-terminal sequence analysis revealed Ser-91 as a major phosphorylation site. Tandem MS revealed a single phosphorylation site at Ser-91. Substitution of Ser-91 with Ala in a synthetic peptide abolished phosphorylation. Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Antibodies raised against a peptide containing phospho-Ser-91 detected phospho-Sept3 only in the cytosol of nerve terminals, whereas Sept3 was located in a peripheral membrane extract. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons. PMID:15107017

  17. Analysis of protein phosphorylation in nerve terminal reveals extensive changes in active zone proteins upon exocytosis

    PubMed Central

    Kohansal-Nodehi, Mahdokht; Chua, John JE; Urlaub, Henning; Jahn, Reinhard; Czernik, Dominika

    2016-01-01

    Neurotransmitter release is mediated by the fast, calcium-triggered fusion of synaptic vesicles with the presynaptic plasma membrane, followed by endocytosis and recycling of the membrane of synaptic vesicles. While many of the proteins governing these processes are known, their regulation is only beginning to be understood. Here we have applied quantitative phosphoproteomics to identify changes in phosphorylation status of presynaptic proteins in resting and stimulated nerve terminals isolated from the brains of Wistar rats. Using rigorous quantification, we identified 252 phosphosites that are either up- or downregulated upon triggering calcium-dependent exocytosis. Particularly pronounced were regulated changes of phosphosites within protein constituents of the presynaptic active zone, including bassoon, piccolo, and RIM1. Additionally, we have mapped kinases and phosphatases that are activated upon stimulation. Overall, our study provides a snapshot of phosphorylation changes associated with presynaptic activity and provides a foundation for further functional analysis of key phosphosites involved in presynaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.14530.001 PMID:27115346

  18. Action of Lambert-Eaton myasthenic syndrome IgG at mouse motor nerve terminals.

    PubMed

    Prior, C; Lang, B; Wray, D; Newsom-Davis, J

    1985-06-01

    We have studied the electrophysiological effects of IgG obtained from four patients with Lambert-Eaton myasthenic syndrome (LEMS) (two with small cell carcinoma), using the mouse passive transfer model. Mice received LEMS or control IgG or plasma, 10 to 60 mg daily. Microelectrode intracellular recordings were made from diaphragm muscle. LEMS IgG and plasma decreased end-plate potential quantal content similarly, confirming IgG as the active factor. LEMS IgG was equally effective in C5-deficient mice, indicating that late complement components are not required. The time course of decline and recovery of quantal content closely followed that of the human IgG in the mouse serum, with time to half-maximal effect of about 1.5 days in each case. Binding/dissociation of IgG or down/up regulation of the antigenic determinants, possibly Ca2+ channels, has a half-life of between 2 and 36 hours. The results confirm our concept that IgG antibody to nerve terminal determinants underlies the disorder of transmitter release in LEMS.

  19. Micromolar-Affinity Benzodiazepine Receptors Regulate Voltage-Sensitive Calcium Channels in Nerve Terminal Preparations

    NASA Astrophysics Data System (ADS)

    Taft, William C.; Delorenzo, Robert J.

    1984-05-01

    Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.

  20. Mitochondrial Calcium Uptake Modulates Synaptic Vesicle Endocytosis in Central Nerve Terminals.

    PubMed

    Marland, Jamie Roslin Keynes; Hasel, Philip; Bonnycastle, Katherine; Cousin, Michael Alan

    2016-01-29

    Presynaptic calcium influx triggers synaptic vesicle (SV) exocytosis and modulates subsequent SV endocytosis. A number of calcium clearance mechanisms are present in central nerve terminals that regulate intracellular free calcium levels both during and after stimulation. During action potential stimulation, mitochondria rapidly accumulate presynaptic calcium via the mitochondrial calcium uniporter (MCU). The role of mitochondrial calcium uptake in modulating SV recycling has been debated extensively, but a definitive conclusion has not been achieved. To directly address this question, we manipulated the expression of the MCU channel subunit in primary cultures of neurons expressing a genetically encoded reporter of SV turnover. Knockdown of MCU resulted in ablation of activity-dependent mitochondrial calcium uptake but had no effect on the rate or extent of SV exocytosis. In contrast, the rate of SV endocytosis was increased in the absence of mitochondrial calcium uptake and slowed when MCU was overexpressed. MCU knockdown did not perturb activity-dependent increases in presynaptic free calcium, suggesting that SV endocytosis may be controlled by calcium accumulation and efflux from mitochondria in their immediate vicinity.

  1. Hyperalgesia induced in the rat by the amino-terminal octapeptide of nerve growth factor.

    PubMed Central

    Taiwo, Y O; Levine, J D; Burch, R M; Woo, J E; Mobley, W C

    1991-01-01

    Nerve growth factor (NGF) in the mouse submandibular gland undergoes cleavage of its amino-terminal octapeptide when salivation is induced by epinephrine. The significance of this event is uncertain; cleaved NGF demonstrates bioactivity and no function has been attributed to the octapeptide produced (NGF-OP; Ser-Ser-Thr-His-Pro-Val-Phe-His). Enzyme inhibition studies indicating structural relatedness of NGF-OP and bradykinin (BK) prompted us to determine whether NGF-OP would elicit BK-like actions. We found that like BK, NGF-OP induced a decrease in mechanical nociceptive threshold (i.e., produced hyperalgesia) in the hairy skin of the rat. This effect was dose-dependent and sequence-specific; like BK it was attenuated by sympathectomy and indomethacin pretreatment. However, NGF-OP actions appeared to be distinct from those for BK in that tissue injury was required for NGF-OP to induce hyperalgesia. Furthermore, we found no evidence that NGF-OP bound to or activated BK receptors. Our data indicate that NGF-OP is a distinct mediator of hyperalgesia. We suggest that NGF-OP alters pain threshold in the injured target regions of NGF-responsive neurons. PMID:1647026

  2. Purinergic modulation of [(3)H]GABA release from rat hippocampal nerve terminals.

    PubMed

    Cunha, R A; Ribeiro, J A

    2000-04-27

    The hippocampal GABAergic system is assumed not to be a target for purine modulation. We have now confirmed that neither adenosine A(1) and A(3) receptor nor nucleotide P(2) or P(4) receptor activation modified the K(+)-evoked [(3)H]GABA release from hippocampal synaptosomes. However, activation of adenosine A(2A) receptors with CGS 21680 (10 nM) or HENECA (30 nM) facilitated GABA release by 32% and 21%, respectively. These effects were prevented by the A(2A) antagonist, ZM 241385 (20 nM). A(2A) receptors may activate adenylate cyclase and protein kinase A since CGS 21680 (10 nM) facilitation was partially prevented by 8-bromo-cAMP (1 mM), forskolin (10 microM) and HA-1004 (10 microM). Protein kinase C may also be recruited, since chelerythrine (6 microM) and phorbol-12, 13-didecanoate (250 nM) attenuated CGS 21680 (10 nM) facilitation of [(3)H]GABA release. Omega-agatoxin-IVA (200 nM) occluded CGS 21680 facilitation suggesting the involvement of P-type calcium channels. Thus, the adenosine A(2A) receptor system appears to be one of the first presynaptic neuromodulatory systems able to enhance the evoked release of GABA from hippocampal nerve terminals.

  3. Brain-derived neurotrophic factor inhibits calcium channel activation, exocytosis, and endocytosis at a central nerve terminal.

    PubMed

    Baydyuk, Maryna; Wu, Xin-Sheng; He, Liming; Wu, Ling-Gang

    2015-03-18

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic function and plasticity and plays important roles in neuronal development, survival, and brain disorders. Despite such diverse and important roles, how BDNF, or more generally speaking, neurotrophins affect synapses, particularly nerve terminals, remains unclear. By measuring calcium currents and membrane capacitance during depolarization at a large mammalian central nerve terminal, the rat calyx of Held, we report for the first time that BDNF slows down calcium channel activation, including P/Q-type channels, and inhibits exocytosis induced by brief depolarization or single action potentials, inhibits slow and rapid endocytosis, and inhibits vesicle mobilization to the readily releasable pool. These presynaptic mechanisms may contribute to the important roles of BDNF in regulating synapses and neuronal circuits and suggest that regulation of presynaptic calcium channels, exocytosis, and endocytosis are potential mechanisms by which neurotrophins achieve diverse neuronal functions.

  4. Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.

    PubMed

    Hassel, Bjørnar; Elsais, Ahmed; Frøland, Anne-Sofie; Taubøll, Erik; Gjerstad, Leif; Quan, Yi; Dingledine, Raymond; Rise, Frode

    2015-05-01

    Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer's disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [(14) C]fructose or its AGE-prone metabolite [(14) C]glyceraldehyde into rat neocortex in vivo led to formation of (14) C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [(14) C]fructose-labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. This was supported by high expression of hexokinase 1, which channels fructose into glycolysis, and whose activity was similar with fructose or glucose as substrates. By contrast, the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only 4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. The genes encoding aldose reductase and sorbitol dehydrogenase, enzymes of the polyol pathway that forms glucose from fructose, were expressed in rat neocortex. These results point to fructose being transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity. We asked how the brain handles fructose, which may react spontaneously with proteins to form 'advanced glycation end products' and trigger inflammation. Neocortical cells took up and metabolized extracellular fructose oxidatively in vivo, and isolated nerve terminals did so in vitro. The low expression of fructose transporter Glut5 limited uptake of extracellular fructose. Hexokinase was a main pathway for fructose metabolism, but ketohexokinase (which leads to glyceraldehyde formation) was

  5. Mechanism of action of ATP on canine pulmonary vagal C fibre nerve terminals.

    PubMed Central

    Pelleg, A; Hurt, C M

    1996-01-01

    1. The effects of extracellular adenosine 5'-triphosphate (ATP) on pulmonary vagal afferent fibres (n = 46) was studied in a canine model in vivo (n = 38). 2. ATP (3-6 mumol kg-1), administered as a rapid bolus into the right atrium, elicited a transient burst of action potentials in cervical vagal fibres, which was not affected by either blockade of ganglionic transmission (hexamethonium) or a drop in arterial blood pressure (nitroglycerine). 3. The fibres with ATP-sensitive terminals were otherwise quiescent with no activity related to either cardiac or respiratory cycles and their conduction velocity was 0.85 +/- 0.13 m s-1 (n = 7). 4. Inflation of the lungs to 2-3 times the tidal volume triggered brief bursts of action potentials in these fibres. 5. Capsaicin (10 micrograms kg-1), given as a rapid bolus into the right atrium, elicited a burst of action potentials in these ATP-sensitive fibres. 6. Smaller amounts of ATP and capsaicin (0.5-3 mumol kg-1 and 1-5 micrograms kg-1, respectively) had similar effects when the two compounds were given into the right pulmonary artery. 7. Adenosine, adenosine 5'-monophosphate, or adenosine 5'-diphosphate did not excite these fibres (n = 30). 8. The non-degradable analogue of ATP alpha,beta-methylene ATP (alpha,beta-mATP) was tenfold more potent than ATP while beta,gamma-methylene ATP (beta,gamma-mATP) was in active. 9. The selective P2x-purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid markedly attenuated the effect of ATP but not of capsaicin. The P2Y-purinoceptor antagonist Reactive Blue 2 was without effect. 10. Pretreatment with pertussis toxin (PTX) did not affect this action of ATP. 11. In the canine lungs ATP activates vagal C fibre nerve terminals. This action is mediated by P2X-purinoceptors and is independent of a PTX-sensitive guanine nucleotide binding protein (G protein). PMID:8745294

  6. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin

    PubMed Central

    Bewick, Guy S.; Banks, Robert W.

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  7. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin.

    PubMed

    Bewick, Guy S; Banks, Robert W

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  8. Pre-synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.

    PubMed

    Martire, Maria; Barrese, Vincenzo; D'Amico, Monia; Iannotti, Fabio Arturo; Pizzarelli, Rocco; Samengo, Irene; Viggiano, Davide; Ruth, Peter; Cherubini, Enrico; Taglialatela, Maurizio

    2010-10-01

    In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large-conductance voltage- and Ca(2+)-dependent K(+) channels (BK channels) in the release of excitatory and non-excitatory neurotransmitters at hippocampal and non-hippocampal sites has been investigated. The results obtained show that the pharmacological modulation of pre-synaptic BK channels selectively regulates [(3)H]D-aspartate release from cortical and hippocampal rat synaptosomes, but it fails to influence the release of excitatory neurotransmitters from cerebellar nerve endings or that of [(3)H]GABA, [(3)H]Noradrenaline, or [(3)H]Dopamine from any of the brain regions investigated. Confocal immunofluorescence experiments in hippocampal or cerebrocortical nerve terminals revealed that the main pore-forming BK α subunit was more abundantly expressed in glutamatergic (vGLUT1(+)) versus GABAergic (GAD(65-67)(+)) nerve terminals. Double patch recordings in monosynaptically connected hippocampal neurons in culture confirmed a preferential control exerted by BK channels on glutamate over GABA release. Altogether, the present results highlight a high degree of specificity in the regulation of the release of various neurotransmitters from distinct brain regions by BK channels, supporting the concept that BK channel modulators can be used to selectively limit excessive excitatory amino acid release, a major pathogenetic mechanism in several neuropsychiatric disorders.

  9. Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea.

    PubMed

    Brock, J A; Pianova, S; Belmonte, C

    2001-06-01

    1. Extracellular recording techniques were used to study nerve terminal impulses (NTIs) recorded from single polymodal nociceptors and cold-sensitive receptors in guinea-pig cornea isolated in vitro. 2. The amplitude and time course of NTIs recorded from polymodal nociceptors was different from those of cold-sensitive receptors. 3. Bath application of tetrodotoxin (1 microM) changed the time course of spontaneous NTIs recorded from both polymodal and cold-sensitive receptors. 4. Bath application of lignocaine (lidocaine; 1-5 mM) abolished all electrical activity. 5. Local application of lignocaine (2.5 and 20 mM) through the recording electrode changed the time course of the NTIs recorded from polymodal nociceptors but not that of NTIs recorded from cold-sensitive nerve endings. 6. It is concluded that action potentials propagate actively in the sensory nerve endings of polymodal nociceptors. In contrast, cold-sensitive receptor nerve endings appear to be passively invaded from a point more proximal in the axon where the action potential can fail or be initiated.

  10. Ultrastructural changes in isolated peptidergic nerve terminals induced by digitonin permeabilization and K+ stimulation in the sinus gland of the crab, Cardisoma carnifex.

    PubMed

    Nordmann, J J; Weatherby, T M; Haylett, B A

    1986-01-01

    The preparation of isolated peptidergic nerve terminals from the sinus gland (a neurohemal organ) of the crab (Cardisoma carnifex) is described. In this species the nerve endings can have diameters up to 30 microns. They release neurosecretory material as judged by the decrease in the volumetric density of granules upon depolarization with potassium. Similar results were obtained after permeabilization of the nerve terminals with digitonin, but only in the presence of micromolar concentrations of calcium. This preparation should prove useful in correlating electrical events with other cellular processes involved in stimulus-secretion coupling.

  11. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    SciTech Connect

    Lin, Tzu-Yu; Lu, Cheng-Wei; Wang, Chia-Chuan; Lu, Jyh-Feng; Wang, Su-Jane

    2012-09-01

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K{sup +} channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca{sup 2+} ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca{sup 2+} concentration ([Ca{sup 2+}]{sub C}), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na{sup +}/Ca{sup 2+} exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca{sup 2+} entry and ERK/synapsin I signaling pathway. -- Highlights: ► Hispidulin inhibited glutamate release from rat

  12. The active zone protein family ELKS supports Ca2+ influx at nerve terminals of inhibitory hippocampal neurons.

    PubMed

    Liu, Changliang; Bickford, Lydia S; Held, Richard G; Nyitrai, Hajnalka; Südhof, Thomas C; Kaeser, Pascal S

    2014-09-10

    In a presynaptic nerve terminal, synaptic vesicle exocytosis is restricted to specialized sites called active zones. At these sites, neurotransmitter release is determined by the number of releasable vesicles and their probability of release. Proteins at the active zone set these parameters by controlling the presynaptic Ca(2+) signal, and through docking and priming of synaptic vesicles. Vertebrate ELKS proteins are enriched at presynaptic active zones, but their functions are not well understood. ELKS proteins are produced by two genes in vertebrates, and each gene contributes ∼50% to total brain ELKS. We generated knock-out mice for ELKS1 and found that its constitutive removal causes lethality. To bypass lethality, and to circumvent redundancy between ELKS1 and ELKS2 in synaptic transmission, we used a conditional genetic approach to remove both genes in cultured hippocampal neurons after synapses are established. Simultaneous removal of ELKS1 and ELKS2 resulted in a 50% decrease of neurotransmitter release at inhibitory synapses, paralleled by a reduction in release probability. Removal of ELKS did not affect synapse numbers or their electron microscopic appearance. Using Ca(2+) imaging, we found that loss of ELKS caused a 30% reduction in single action potential-triggered Ca(2+) influx in inhibitory nerve terminals, consistent with the deficits in synaptic transmission and release probability. Unlike deletion of the active zone proteins RIM, RIM-BP, or bruchpilot, ELKS removal did not lead to a measurable reduction in presynaptic Ca(2+) channel levels. Our results reveal that ELKS is required for normal Ca(2+) influx at nerve terminals of inhibitory hippocampal neurons.

  13. The Active Zone Protein Family ELKS Supports Ca2+ Influx at Nerve Terminals of Inhibitory Hippocampal Neurons

    PubMed Central

    Liu, Changliang; Bickford, Lydia S.; Held, Richard G.; Nyitrai, Hajnalka

    2014-01-01

    In a presynaptic nerve terminal, synaptic vesicle exocytosis is restricted to specialized sites called active zones. At these sites, neurotransmitter release is determined by the number of releasable vesicles and their probability of release. Proteins at the active zone set these parameters by controlling the presynaptic Ca2+ signal, and through docking and priming of synaptic vesicles. Vertebrate ELKS proteins are enriched at presynaptic active zones, but their functions are not well understood. ELKS proteins are produced by two genes in vertebrates, and each gene contributes ∼50% to total brain ELKS. We generated knock-out mice for ELKS1 and found that its constitutive removal causes lethality. To bypass lethality, and to circumvent redundancy between ELKS1 and ELKS2 in synaptic transmission, we used a conditional genetic approach to remove both genes in cultured hippocampal neurons after synapses are established. Simultaneous removal of ELKS1 and ELKS2 resulted in a 50% decrease of neurotransmitter release at inhibitory synapses, paralleled by a reduction in release probability. Removal of ELKS did not affect synapse numbers or their electron microscopic appearance. Using Ca2+ imaging, we found that loss of ELKS caused a 30% reduction in single action potential-triggered Ca2+ influx in inhibitory nerve terminals, consistent with the deficits in synaptic transmission and release probability. Unlike deletion of the active zone proteins RIM, RIM-BP, or bruchpilot, ELKS removal did not lead to a measurable reduction in presynaptic Ca2+ channel levels. Our results reveal that ELKS is required for normal Ca2+ influx at nerve terminals of inhibitory hippocampal neurons. PMID:25209271

  14. Preferred sites of exocytosis and endocytosis colocalize during high but not lower frequency stimulation in mouse motor nerve terminals

    PubMed Central

    Gaffield, Michael A.; Tabares, Lucia; Betz, William J.

    2010-01-01

    The spatial relationship of exocytosis and endocytosis in motor nerve terminals has been explored, with varied results, mostly in fixed preparations and without direct information on the utilization of each exocytic site. We sought to determine these spatial properties in real time using synaptopHluorin (spH) and FM 4-64. Earlier we showed that nerve stimulation elicits the appearance of spH fluorescence hot spots, which mark preferred sites of exocytosis. Here we show that nerve stimulation in the presence of the styryl dye FM 4-64 evokes hot spots of FM 4-64 fluorescence. Their size, density, and rate of appearance are similar to the spH hot spots, but their rate of disappearance after stimulation was much slower (t½ ∼9 min versus ∼10 s for spH hot spots), consistent with FM 4-64 spots identifying bulk endocytosis and subsequent slow intracellular dispersion of nascent vesicles. Simultaneous imaging of both fluorophores revealed a strong colocalization of spH and FM 4-64 spots, but only during high (100 Hz) stimulation. At 40 Hz stimulation, exo- and endocytic spots did not colocalize. Our results are consistent with the hypothesis that hot spots of endocytosis, possibly in the form of bulk uptake, occur at or very near highly active exocytic sites during high frequency stimulation. PMID:19955383

  15. The effects of combined application of inorganic Martian dust simulant and carbon dots on glutamate transport rat brain nerve terminals

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Krisanova, Natalia; Nazarova, Anastasiya; Borysov, Arseniy; Pastukhov, Artem; Pozdnyakova, Natalia; Dudarenko, Marina

    2016-07-01

    During inhalation, nano-/microsized particles are efficiently deposited in nasal, tracheobronchial, and alveolar regions and can be transported to the central nervous system (Oberdorster et al., 2004). Recently, the research team of this study found the minor fractions of nanoparticles with the size ~ 50 -60 nm in Lunar and Martian dust stimulants (JSC-1a and JSC, ORBITEC Orbital Technologies Corporation, Madison, Wisconsin), whereas the average size of the simulants was 1 mm and 4mm, respectively (Krisanova et al., 2013). Also, the research team of this study discovered new phenomenon - the neuromodulating and neurotoxic effect of carbon nano-sized particles - Carbon dots (C-dots), originated from ash of burned carbon-containing product (Borisova et al, 2015). The aims of this study was to analyse acute effects of upgraded stimulant of inorganic Martian dust derived from volcanic ash (JSC-1a/JSC, ORBITEC Orbital Technologies Corporation, Madison, Wisconsin) by the addition of carbon components, that is, carbon dots, on the key characteristic of synaptic neurotransmission. Acute administration of carbon-containing Martian dust analogue resulted in a significant decrease in transporter-mediated uptake of L-[14C]glutamate (the major excitatory neurotransmitter) by isolated rat brain nerve terminals. The ambient level of the neurotransmitter in the preparation of nerve terminals increased in the presence of carbon dot-contained Martian dust analogue. These effects were associated with action of carbon component of the upgraded Martian dust stimulant but not with its inorganic constituent.

  16. Interaction of /sup 125/I-labeled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves

    SciTech Connect

    Black, J.D.; Dolly, J.O.

    1986-01-01

    The labeling patterns produced by radioiodinated botulinum neurotoxin (/sup 125/I-BoNT) types A and B at the vertebrate neuromuscular junction were investigated using electron microscopic autoradiography. The data obtained allow the following conclusions to be made. (a) /sup 125/I-BoNT type A, applied in vivo or in vitro to mouse diaphragm or frog cutaneous pectoris muscle, interacts saturably with the motor nerve terminal only; silver grains occur on the plasma membrane, within the synaptic bouton, and in the axoplasm of the nerve trunk, suggesting internalization and retrograde intra-axonal transport of toxin or fragments thereof. (b) /sup 125/I-BoNT type B, applied in vitro to the murine neuromuscular junction, interacts likewise with the motor nerve terminal except that a lower proportion of internalized radioactivity is seen. This result is reconcilable with the similar, but not identical, pharmacological action of these toxin types. (c) The saturability of labeling in each case suggested the involvement of acceptors; on preventing the internalization step with metabolic inhibitors, their precise location became apparent. They were found on all unmyelinated areas of the nerve terminal membrane, including the preterminal axon and the synaptic bouton. (d) It is not proposed that these membrane acceptors target BoNT to the nerve terminal and mediate its delivery to an intracellular site, thus contributing to the toxin's selective inhibitory action on neurotransmitter release.

  17. A Ca2+-induced Ca2+ Release Mechanism Involved in Asynchronous Exocytosis at Frog Motor Nerve Terminals

    PubMed Central

    Narita, K.; Akita, T.; Osanai, M.; Shirasaki, T.; Kijima, H.; Kuba, K.

    1998-01-01

    The extent to which Ca2+-induced Ca2+ release (CICR) affects transmitter release is unknown. Continuous nerve stimulation (20–50 Hz) caused slow transient increases in miniature end-plate potential (MEPP) frequency (MEPP-hump) and intracellular free Ca2+ ([Ca2+]i) in presynaptic terminals (Ca2+-hump) in frog skeletal muscles over a period of minutes in a low Ca2+, high Mg2+ solution. Mn2+ quenched Indo-1 and Fura-2 fluorescence, thus indicating that stimulation was accompanied by opening of voltage-dependent Ca2+ channels. MEPP-hump depended on extracellular Ca2+ (0.05–0.2 mM) and stimulation frequency. Both the Ca2+- and MEPP-humps were blocked by 8-(N,N-diethylamino)octyl3,4,5-trimethoxybenzoate hydrochloride (TMB-8), ryanodine, and thapsigargin, but enhanced by CN−. Thus, Ca2+-hump is generated by the activation of CICR via ryanodine receptors by Ca2+ entry, producing MEPP-hump. A short interruption of tetanus (<1 min) during MEPP-hump quickly reduced MEPP frequency to a level attained under the effect of TMB-8 or thapsigargin, while resuming tetanus swiftly raised MEPP frequency to the previous or higher level. Thus, the steady/equilibrium condition balancing CICR and Ca2+ clearance occurs in nerve terminals with slow changes toward a greater activation of CICR (priming) during the rising phase of MEPP-hump and toward a smaller activation during the decay phase. A short pause applied after the end of MEPP- or Ca2+-hump affected little MEPP frequency or [Ca2+]i, but caused a quick increase (faster than MEPP- or Ca2+-hump) after the pause, whose magnitude increased with an increase in pause duration (<1 min), suggesting that Ca2+ entry-dependent inactivation, but not depriming process, explains the decay of the humps. The depriming process was seen by giving a much longer pause (>1 min). Thus, ryanodine receptors in frog motor nerve terminals are endowed with Ca2+ entry-dependent slow priming and fast inactivation mechanisms, as well as Ca2+ entry

  18. Neurotransmitter release from tottering mice nerve terminals with reduced expression of mutated P- and Q-type Ca2+-channels.

    PubMed

    Leenders, A G Miriam; van den Maagdenberg, Arn M J M; Lopes da Silva, Fernando H; Sheng, Zu-Hang; Molenaar, Peter C; Ghijsen, Wim E J M

    2002-01-01

    Neurotransmitter release is triggered by Ca2+-influx through multiple sub-types of high voltage-activated Ca2+-channels. Tottering mice have a mutation in the alpha1A pore-forming subunit of P- and Q-type Ca2+-channels, two prominent sub-types that regulate transmitter release from central nerve terminals. Immunoblotting analysis of purified forebrain terminals from tottering mice revealed an 85% reduction in the protein expression level of the mutated alpha1A subunit compared to expression of the alpha1A subunit in wild-type terminals. In contrast, the expression of the alpha1B subunit of the N-type Ca2+-channels was unchanged. Release of the amino acids glutamate and GABA and of the neuropeptide cholecystokinin (CCK) induced by a short (100 ms) depolarization pulse was unchanged in the terminals of tottering mice. Studies using specific blockers of Ca2+-channels however, revealed a reduced contribution of P- and Q-type Ca2+-channels to glutamate and cholecystokinin release, whereas a greater reliance on N-type Ca2+-channels for release of these transmitters was observed. In contrast, the contribution of the P-, Q- and N-type Ca2+-channels to the release of GABA was not altered in tottering mice. These results indicate that the expression of the alpha1A subunit was decreased in terminals from tottering mice, and that a decreased contribution of P- and Q-type Ca2+-channels to the release of glutamate and cholecystokinin was functionally compensated by an increased contribution of N-type Ca2+-channels.

  19. Patch-clamp capacitance measurements and Ca²⁺ imaging at single nerve terminals in retinal slices.

    PubMed

    Kim, Mean-Hwan; Vickers, Evan; von Gersdorff, Henrique

    2012-01-01

    in agar (or placed onto a filter paper) and then sliced. In this video, we employ the pre-embedding agar technique using goldfish retina. Some of the giant bipolar cell terminals in our slices of goldfish retina are axotomized (axon-cut) during the slicing procedure. This allows us to isolate single presynaptic nerve terminal inputs, because recording from axotomized terminals excludes the signals from the soma-dendritic compartment. Alternatively, one can also record from intact Mb bipolar cells, by recording from terminals attached to axons that have not been cut during the slicing procedure. Overall, use of this experimental protocol will aid in studies of retinal synaptic physiology, microcircuit functional analysis, and synaptic transmission at ribbon synapses. PMID:22297269

  20. The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin.

    PubMed

    Bulc, Michał; Lewczuk, Bogdan; Prusik, Magdalena; Całka, Jarosław

    2013-05-01

    Innervation of the mammalian pineal gland during prenatal development is poorly recognized. Therefore, immunofluorescence studies of the pineals of 70- and 90-day-old foetuses of the domestic pig were performed using antibodies against tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH), neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON). The investigated glands were supplied by numerous nerve fibres containing TH and DβH. The density of these fibres was higher in the distal and middle parts of the gland than in the proximal one. NPY and CPON were identified in the majority of DβH-positive fibres as well as in a small population of DβH-negative fibres localized mainly in the proximal part of the pineal. The immunoreactive fibres were more numerous in 90-day-old foetuses than in 70-day-old ones. The effect of norepinephrine on melatonin secretion by the foetal pineals in the short-term organ culture was studied to determine the role of DβH-positive fibres during prenatal life. For the same purpose melatonin was measured in the blood in the umbilical cords and in the jugular vein of the mother. The pineals of both groups of foetuses did not secrete melatonin in the organ culture, independently of the presence or absence of norepinephrine in the medium. Melatonin concentrations in the blood in the umbilical cords of foetuses from the same litter and in the jugular vein of their mother were similar. The presence of adrenergic nerve fibres in the pig pineal during gestation does not seem to be associated with the control of melatonin secretion.

  1. Early Exposure to General Anesthesia Disrupts Spatial Organization of Presynaptic Vesicles in Nerve Terminals of the Developing Rat Subiculum.

    PubMed

    Lunardi, N; Oklopcic, A; Prillaman, M; Erisir, A; Jevtovic-Todorovic, V

    2015-10-01

    Exposure to general anesthesia (GA) during critical stages of brain development induces widespread neuronal apoptosis and causes long-lasting behavioral deficits in numerous animal species. Although several studies have focused on the morphological fate of neurons dying acutely by GA-induced developmental neuroapoptosis, the effects of an early exposure to GA on the surviving synapses remain unclear. The aim of this study is to study whether exposure to GA disrupts the fine regulation of the dynamic spatial organization and trafficking of synaptic vesicles in presynaptic terminals. We exposed postnatal day 7 (PND7) rat pups to a clinically relevant anesthetic combination of midazolam, nitrous oxide, and isoflurane and performed a detailed ultrastructural analysis of the synaptic vesicle architecture at presynaptic terminals in the subiculum of rats at PND 12. In addition to a significant decrease in the density of presynaptic vesicles, we observed a reduction of docked vesicles, as well as a reduction of vesicles located within 100 nm from the active zone, in animals 5 days after an initial exposure to GA. We also found that the synaptic vesicles of animals exposed to GA are located more distally with respect to the plasma membrane than those of sham control animals and that the distance between presynaptic vesicles is increased in GA-exposed animals compared to sham controls. We report that exposure of immature rats to GA during critical stages of brain development causes significant disruption of the strategic topography of presynaptic vesicles within the nerve terminals of the subiculum. PMID:26048670

  2. The spatial pattern of exocytosis and post-exocytic mobility of synaptopHluorin in mouse motor nerve terminals

    PubMed Central

    Gaffield, Michael A; Tabares, Lucia; Betz, William J

    2009-01-01

    We monitored the spatial distribution of exo- and endocytosis at 37°C in mouse motor nerve terminals expressing synaptopHluorin (spH), confirming and extending earlier work at room temperature, which had revealed fluorescent ‘hot spots’ appearing in repeatable locations during tetanic stimulation. We also tested whether hot spots appeared during mild stimulation. Averaged responses from single shocks showed a clear fluorescence jump, but revealed no sign of hot spots; instead, fluorescence rose uniformly across the terminal. Only after 5–25 stimuli given at high frequency did hot spots appear, suggesting a novel initiation mechanism. Experiments showed that about half of the surface spH molecules were mobile, and that spH movement occurred out of hot spots, demonstrating their origin as exocytic sources, not endocytic sinks. Taken together, our results suggest that synaptic vesicles exocytose equally throughout the terminal with mild stimulation, but preferentially exocytose at specific, repeatable locations during tetanic stimulation. PMID:19153160

  3. A novel large-conductance Ca(2+)-activated potassium channel and current in nerve terminals of the rat neurohypophysis.

    PubMed Central

    Wang, G; Thorn, P; Lemos, J R

    1992-01-01

    1. Nerve terminals of the rat posterior pituitary were acutely dissociated and identified using a combination of morphological and immunohistochemical techniques. Terminal membrane currents were studied using the 'whole-cell' patch clamp technique and channels were studied using inside-out and outside-out patches. 2. In physiological solutions, but with 7 mM 4-aminopyridine (4-AP), depolarizing voltage clamp steps from different holding potentials (-90 or -50 mV) elicited a fast, inward current followed by a slow, sustained, outward current. This outward current did not appear to show any steady-state inactivation. 3. The threshold for activation of the outward current was -30 mV and the current-voltage relation was 'bell-shaped'. The amplitude increased with increasingly depolarized potential steps. The outward current reversal potential was measured using tail current analysis and was consistent with that of a potassium current. 4. The sustained potassium current was determined to be dependent on the concentration of intracellular calcium. Extracellular Cd2+ (80 microM), a calcium channel blocker, also reversibly abolished the outward current. 5. The current was delayed in onset and was sustained over the length of a 150 ms-duration depolarizing pulse. The outward current reached a peak plateau and then decayed slowly. The decay was fitted by a single exponential with a time constant of 9.0 +/- 2.2 s. The decay constants did not show a dependence on voltage but rather on intracellular Ca2+. The time course of recovery from this decay was complex with full recovery taking > 190 s. 6. 4-AP (7 mM), dendrotoxin (100 nM), apamin (40-80 nM), and charybdotoxin (10-100 nM) had no effect on the sustained outward current. In contrast Ba2+ (200 microM) and tetraethylammonium inhibited the current, the latter in a dose-dependent manner (apparent concentration giving 50% of maximal inhibition (IC50) = 0.51 mM). 7. The neurohypophysial terminal outward current recorded here

  4. Non-myelinated nerve fibres and their terminals in the sub-odontoblastic plexus of the feline dental pulp.

    PubMed Central

    Holland, G R

    1980-01-01

    Serial thin sections of the coronal dental pulp of the cat's canine tooth were cut. Parts of the sub-odontoblastic neural plexus were photographed from 100 of the sections. The plexus consists of many slender, predominantly unmyelinated nerve fibres. Many axons are incompletely sheathed by their Schwann cell. Some axons leave the Schwann cell sheath and either end in the extracellar space or return to the Schwann cell after traveling a short distance. Several axons are often seen in close contact within a single invagination of the Schwann cell. They remain in contact for up to 7 micrometer.l Both Schwann cells and axons are see to branch in this region. These features may be characteristic of nerve fibres and terminals which respond to noxious stimuli. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Figs. 7-8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 PMID:7410190

  5. Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins

    NASA Technical Reports Server (NTRS)

    Kashani, A. H.; Chen, B. M.; Grinnell, A. D.

    2001-01-01

    Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins.The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds.There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other.There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation.

  6. Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation.

    PubMed

    Meunier, Frédéric A; Lisk, Godfrey; Sesardic, Dorothea; Dolly, J Oliver

    2003-04-01

    Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery.

  7. Spatial facilitation and depression within one motor nerve terminal of frogs.

    PubMed Central

    Dudel, J; Parnas, I; Parnas, H

    1993-01-01

    1. Perfused macropatch electrodes were used to stimulate and simultaneously measure release from two sites on the same terminal of the frog cutaneous pectoris muscle. 2. It was found that release occurring at one site often affected release at an adjacent site 50 microns away, either enhancing it ('spatial facilitation') or depressing it ('spatial depression'). Spatial facilitation (or depression) was defined as the release produced by a test pulse at the second site (test electrode) when preceded by a pulse at the first site (prepulse electrode) divided by the release produced by the test pulse alone. 3. Spatial facilitation varied with the time interval between the prepulse and the test pulse. Peak spatial facilitation, which on the average was 2.14, occurred with an interval of 1-3 ms. With longer intervals spatial facilitation decayed with a time constant between 3-6 ms. When the time interval between the prepulse and the test pulse was zero (no delay), the release after the test pulse was always depressed. 4. When Ca2+ was omitted from the perfusate of the prepulse electrode, spatial facilitation was abolished. When a brief hyperpolarizing pulse followed the depolarizing prepulse with zero delay spatial facilitation was also abolished. 5. Electrotonic spread or Ca2+ diffusion within the axon terminal are excluded as coupling agents for spatial facilitation. It is suggested that the coupling agent may possibly be related to a hypothetical release-promoting factor. Images Fig. 1 PMID:8350260

  8. Computational Modeling Reveals Optimal Strategy for Kinase Transport by Microtubules to Nerve Terminals

    PubMed Central

    Koon, Yen Ling; Koh, Cheng Gee; Chiam, Keng-Hwee

    2014-01-01

    Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase) transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration. PMID:24691408

  9. Regulation and function of the alpha/sub 2/ adrenergic autoreceptor in the central nervous system

    SciTech Connect

    Spengler, R.N.

    1987-01-01

    The purpose of this investigation was to determine whether changes observed in the number of alpha/sub 2/ adrenergic receptors in the brain as measured by radioligand binding experiments reflect changes in the function of alpha/sub 2/ autoregulatory receptors which are located on noradrenergic nerve terminals. Inhibition by clonidine of field stimulated /sup 3/H-norepinephrine (/sup 3/H-NE) release from rat hippocampal slices before and after several drug treatments was analyzed to investigate changes in alpha/sub 2/ adrenergic receptor function. Clonidine in a concentration-dependent manner inhibited /sup 3/H-NE release. The effect of clonidine was blocked by the specific alpha/sub 2/ adrenergic receptor antagonist, idazoxan. The cumulative administration of clonidine generated a smooth and well-fitted log-concentration-effect curve. Results are presented which demonstrate that this technique can be employed to investigate the role of changes in the function of the alpha/sub 2/ autoregulatory receptor. The present investigation also examined representatives of four drug classes which have been shown to alter the specific binding of /sup 3/H-clonidine to neural membranes to determine whether changes in the alpha/sub 2/ autoregulatory receptor function also occur.

  10. α-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve Terminals

    PubMed Central

    Wu, Xin-Sheng; Sheng, Jiansong; Zhang, Zhen; Yue, Hai-Yuan; Sun, Lixin; Sgobio, Carmelo; Lin, Xian; Peng, Shiyong; Jin, Yinghui; Gan, Lin; Wu, Ling-Gang

    2016-01-01

    α-Synuclein (α-syn) missense and multiplication mutations have been suggested to cause neurodegenerative diseases, including Parkinson's disease (PD) and dementia with Lewy bodies. Before causing the progressive neuronal loss, α-syn mutations impair exocytosis, which may contribute to eventual neurodegeneration. To understand how α-syn mutations impair exocytosis, we developed a mouse model that selectively expressed PD-related human α-syn A53T (h-α-synA53T) mutation at the calyx of Held terminals, where release mechanisms can be dissected with a patch-clamping technique. With capacitance measurement of endocytosis, we reported that h-α-synA53T, either expressed transgenically or dialyzed in the short term in calyces, inhibited two of the most common forms of endocytosis, the slow and rapid vesicle endocytosis at mammalian central synapses. The expression of h-α-synA53T in calyces also inhibited vesicle replenishment to the readily releasable pool. These findings may help to understand how α-syn mutations impair neurotransmission before neurodegeneration. SIGNIFICANCE STATEMENT α-Synuclein (α-syn) missense or multiplication mutations may cause neurodegenerative diseases, such as Parkinson's disease and dementia with Lewy bodies. The initial impact of α-syn mutations before neuronal loss is impairment of exocytosis, which may contribute to eventual neurodegeneration. The mechanism underlying impairment of exocytosis is poorly understood. Here we report that an α-syn mutant, the human α-syn A53T, inhibited two of the most commonly observed forms of endocytosis, slow and rapid endocytosis, at a mammalian central synapse. We also found that α-syn A53T inhibited vesicle replenishment to the readily releasable pool. These results may contribute to accounting for the widely observed early synaptic impairment caused by α-syn mutations in the progression toward neurodegeneration. PMID:27098685

  11. Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

    PubMed Central

    Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu-Kuei

    2013-01-01

    Abstract This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca2+ ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca2+ concentration, but did not alter 4-AP–mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry. PMID:23342970

  12. Neurogenic Inflammation in Stress-Induced Termination of Murine Hair Growth Is Promoted by Nerve Growth Factor

    PubMed Central

    Peters, Eva Milena J.; Handjiski, Bori; Kuhlmei, Arne; Hagen, Evelin; Bielas, Hannes; Braun, Armin; Klapp, Burghard F.; Paus, Ralf; Arck, Petra Clara

    2004-01-01

    Recently, we have revealed the existence of a “brain-hair follicle axis” in murine skin and have identified the neuropeptide substance P (SP) as a key mediator of stress-induced hair growth inhibition in vivo. Published evidence suggests that increased numbers of SP-immunoreactive sensory fibers, as seen in the dermis of stressed mice in anagen-catagen transition, are a result of transient high levels of nerve growth factor (NGF). Thus, we now aimed at dissecting the role of NGF in stress-triggered hair growth termination in our murine model. By real time PCR and immunohistochemistry, stress-exposed mice showed an up-regulation of NGF and its low-affinity receptor p75NTR; the NGF high-affinity receptor TrkA was moderately down-regulated. On neutralization of NGF, premature onset of catagen, apoptosis, and increased number/activation of perifollicular mast cells and antigen-presenting cells, which reflects the skin response to stress, was significantly abrogated. Stress or subcutaneous injection of recombinant NGF (to mimic stress) resulted in an increased percentage of SP+ neurons in dorsal root ganglia, as measured by retrograde tracing. Taken together, these data suggest that NGF is a central element in the perifollicular neurogenic inflammation that develops during the murine skin response to stress and antagonizing NGF may be a promising therapeutic approach to counter the negative effect of stress on hair growth. PMID:15215181

  13. Targeted delivery into motor nerve terminals of inhibitors for SNARE-cleaving proteases via liposomes coupled to an atoxic botulinum neurotoxin.

    PubMed

    Edupuganti, Om P; Ovsepian, Saak V; Wang, Jiafu; Zurawski, Tomas H; Schmidt, James J; Smith, Leonard; Lawrence, Gary W; Dolly, J Oliver

    2012-07-01

    A targeted drug carrier (TDC) is described for transferring functional proteins or peptides into motor nerve terminals, a pivotal locus for therapeutics to treat neuromuscular disorders. It exploits the pronounced selectivity of botulinum neurotoxin type B (BoNT/B) for interacting with acceptors on these cholinergic nerve endings and becoming internalized. The gene encoding an innocuous BoNT/B protease-inactive mutant (BoTIM) was fused to that for core streptavidin, expressed in Escherichia coli and the purified protein was conjugated to surface-biotinylated liposomes. Such decorated liposomes, loaded with fluorescein as traceable cargo, acquired pronounced specificity for motor nerve terminals in isolated mouse hemidiaphragms and facilitated the intraneuronal transfer of the fluor, as revealed by confocal microscopy. Delivery of the protease light chain of botulinum neurotoxin type A (BoNT/A) via this TDC accelerated the onset of neuromuscular paralysis, indicative of improved translocation of this enzyme into the presynaptic cytosol with subsequent proteolytic inactivation of synaptosomal-associated protein of molecular mass 25 kDa (SNAP-25), an exocytotic soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) essential for neurotransmitter release. BoTIM-coupled liposomes, loaded with peptide inhibitors of proteases, yielded considerable attenuation of the neuroparalytic effects of BoNT/A or BoNT/F as a result of their cytosolic transfer, the first in situ demonstration of the ability of designer antiproteases to suppress the symptoms of botulism ex vivo. Delivery of the BoNT/A inhibitor by liposomes targeted with the full-length BoTIM proved more effective than that mediated by its C-terminal neuroacceptor-binding domain. This demonstrated versatility of TDC for nonviral cargo transfer into cholinergic nerve endings has unveiled its potential for direct delivery of functional targets into motor nerve endings.

  14. Physiological and Clinical Implications of Adrenergic Pathways at High Altitude.

    PubMed

    Richalet, Jean-Paul

    2016-01-01

    The adrenergic system is part of a full array of mechanisms allowing the human body to adapt to the hypoxic environment. Triggered by the stimulation of peripheral chemoreceptors, the adrenergic centers in the medulla are activated in acute hypoxia and augment the adrenergic drive to the organs, especially to the heart, leading to tachycardia. With prolonged exposure to altitude hypoxia, the adrenergic drive persists, as witnessed by elevated blood concentrations of catecholamines and nerve activity in adrenergic fibers. In response to this persistent stimulation, the pathways leading to the activation of adenylate cyclase are modified. A downregulation of β-adrenergic and adenosinergic receptors is observed, while muscarinic receptors are upregulated. The expression and activity of Gi and Gs proteins are modified, leading to a decreased response of adenylate cyclase activity to adrenergic stimulation. The clinical consequences of these cellular and molecular changes are of importance, especially for exercise performance and protection of heart function. The decrease in maximal exercise heart rate in prolonged hypoxia is fully accounted for the observed changes in adrenergic and muscarinic pathways. The decreased heart rate response to isoproterenol infusion is another marker of the desensitization of adrenergic pathways. These changes can be considered as mechanisms protecting the heart from a too high oxygen consumption in conditions where the oxygen availability is severely reduced. Similarly, intermittent exposure to hypoxia has been shown to protect the heart from an ischemic insult with similar mechanisms involving G proteins and downregulation of β receptors. Other pathways with G proteins are concerned in adaptation to hypoxia, such as lactate release by the muscles and renal handling of calcium. Altogether, the activation of the adrenergic system is useful for the acute physiological response to hypoxia. With prolonged exposure to hypoxia, the autonomous

  15. Comparison of nerve terminal events in vivo effecting retrograde transport of vesicles containing neurotrophins or synaptic vesicle components.

    PubMed

    Weible, M W; Ozsarac, N; Grimes, M L; Hendry, I A

    2004-03-15

    Although vesicular retrograde transport of neurotrophins in vivo is well established, relatively little is known about the mechanisms that underlie vesicle endocytosis and formation before transport. We demonstrate that in vivo not all retrograde transport vesicles are alike, nor are they all formed using identical mechanisms. As characterized by density, there are at least two populations of vesicles present in the synaptic terminal that are retrogradely transported along the axon: those containing neurotrophins (NTs) and those resulting from synaptic vesicle recycling. Vesicles containing nerve growth factor (NGF), NT-3, or NT-4 had similar densities with peak values at about 1.05 g/ml. Synaptic-derived vesicles, labeled with anti-dopamine beta-hydroxylase (DBH), had densities with peak values at about 1.16 g/ml. We assayed the effects of pharmacologic agents in vivo on retrograde transport from the anterior eye chamber to the superior cervical ganglion. Inhibitors of phosphatidylinositol-3-OH (PI-3) kinase and actin function blocked transport of both anti-DBH and NGF, demonstrating an essential role for these molecules in retrograde transport of both vesicle types. Dynamin, a key element in synaptic vesicle recycling, was axonally transported in retrograde and anterograde directions, and compounds able to interfere with dynamin function had a differential effect on retrograde transport of NTs and anti-DBH. Okadaic acid significantly decreased retrograde axonal transport of anti-DBH and increased NGF retrograde transport. We conclude that there are both different and common proteins involved in endocytosis and targeting of retrograde transport of these two populations of vesicles. PMID:14994338

  16. Differing effects of transport inhibitor on glutamate uptake by nerve terminals before and after exposure of rats to artificial gravity.

    NASA Astrophysics Data System (ADS)

    Borisova, T.; Krisanova, N.; Himmelreich, N.

    Glutamate is the major excitatory neurotransmitter in the brain. Subsequent to its release from glutamatergic neurons and activation of receptors, it is removed from extracellular space by high affinity Na^+-dependent glutamate transporters, which utilize the Na^+/K^+ electrochemical gradient as a driving force and located in nerve terminals and astrocytes. The glutamate transporters may modify the time course of synaptic events. Like glutamate itself, glutamate transporters are somehow involved in almost all aspects of normal and abnormal brain activity (e.g. cerebral ischemia, amyotrophic lateral sclerosis, Alzheimer's disease, traumatic brain injury, epilepsy and schizophrenia). The present study assessed transporter inhibitor for the ability to inhibit glutamate uptake by synaptosomes at the normal and hypergravity conditions (rats were rotated in a long-arm centrifuge at ten-G during one-hour period). DL-threo-beta-benzyloxyaspartate (DL-TBOA) is a newly developed competitive inhibitor of the high-affinity, Na^+-dependent glutamate transporters. As a potent, non- transported inhibitor of glutamate transporters, DL-TBOA promises to be a valuable new compound for the study of glutamatergic mechanisms. We demonstrated that DL-TBOA inhibited glutamate uptake ( 100 μM glutamate, 30 sec incubation period) in dose-dependent manner as in control as in hypergravity. The effect of this transport inhibitor on glutamate uptake by control synaptosomes and synaptosomes prepared of animals exposed to hypergravity was different. IC50 values calculated on the basis of curves of non-linear regression kinetic analysis was 18±2 μM and 11±2 μM ((P≤0,05) before and after exposure to artificial gravity, respectively. Inhibition caused by 10 μM DL-TBOA was significantly increased from 38,0±3,8 % in control group to 51,0±4,1 % in animals, exposed to hypergravity (P≤0,05). Thus, DL-TBOA had complex effect on glutamate uptake process and perhaps, became more potent under

  17. Age-related decrease of the chorda tympani nerve terminal field in the nucleus of the solitary tract is prevented by dietary sodium restriction during development.

    PubMed

    Sollars, S I; Walker, B R; Thaw, A K; Hill, D L

    2006-01-01

    Institution of a low-NaCl diet beginning at embryonic day 3 and continued throughout pre- and postnatal development has widespread effects on the neuroanatomical organization of the first gustatory relay in the nucleus of the solitary tract. To determine when these effects are expressed postnatally, the terminal field of the chorda tympani nerve was compared between sodium-restricted and sodium-replete rats at postnatal days 15-17, postnatal days 25-27, postnatal days 35-37, and adults. Total terminal fields were significantly larger in postnatal days 35-37 and adult sodium-restricted rats compared with aged-matched controls. The group-related differences appear related more to a remodeling of the terminal field in the dorsal zone of the terminal field in controls. Specifically, the terminal field volume in the dorsal zone in controls decreased dramatically from postnatal days 25-27 to postnatal days 35-37 and then again from postnatal days 35-37 to adulthood. In contrast, the fields did not change during development in sodium-restricted rats. These findings suggest that remodeling of the chorda tympani field occurs in controls at about the developmental period of taste response maturation. The lack of remodeling in sodium-restricted rats may be explained by a corresponding lack of functional response development to sodium salts. These results also illustrate the specificity and extent of how early dietary manipulations shape the developing brainstem.

  18. Neurotoxic Potential of Lunar and Martian Dust: Influence on Em, Proton Gradient, Active Transport, and Binding of Glutamate in Rat Brain Nerve Terminals

    PubMed Central

    Krisanova, Natalia; Kasatkina, Ludmila; Sivko, Roman; Borysov, Arseniy; Nazarova, Anastasiya; Slenzka, Klaus; Borisova, Tatiana

    2013-01-01

    Abstract The harmful effects of lunar dust (LD) on directly exposed tissues are documented in the literature, whereas researchers are only recently beginning to consider its effects on indirectly exposed tissues. During inhalation, nano-/microsized particles are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of LD and martian dust (MD) has not yet been assessed. Glutamate is the main excitatory neurotransmitter involved in most aspects of normal brain function, whereas disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The research was focused on the analysis of the effects of LD/MD simulants (JSC-1a/JSC, derived from volcanic ash) on the key characteristics of glutamatergic neurotransmission. The average size of LD and MD particles (even minor fractions) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled l-[14C]glutamate, it was shown that there is an increase in l-[14C]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Na+] media and at low temperature in the presence of LD. MD caused significantly lesser changes under the same conditions, whereas nanoparticles of magnetite had no effect at all. Fluorimetric experiments with potential-sensitive dye rhodamine 6G and pH-sensitive dye acridine orange showed that the potential of the plasma membrane of the nerve terminals and acidification of synaptic vesicles were not altered by LD/MD (and nanoparticles of magnetite). Thus, the unique effect of LD to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on extracellular glutamate homeostasis in the central nervous system and cause alterations in the ambient level of glutamate, which is extremely important for proper synaptic transmission. During a long-term mission, a combination of constant irritation

  19. The cholinergic blocking action of adrenergic blocking agents in the pharmacological analysis of autonomic innervation

    PubMed Central

    Boyd, Helen; Burnstock, G.; Campbell, G.; Jowett, Alison; O'Shea, Judith; Wood, Margaret

    1963-01-01

    The adrenergic blocking agents tolazoline, phentolamine, piperoxan, yohimbine, phenoxybenzamine, bretylium and guanethidine block the excitatory actions both of cholinergic nerves and of added acetylcholine on a variety of vertebrate smooth muscle preparations. These cholinergic blocking actions often occurred with concentrations lower than those required to block the response of the guinea-pig vas deferens to stimulation of the adrenergic hypogastric nerve. The anti-acetylcholine activities of these drugs have been studied in detail, using the guinea-pig rectum and the toad bladder as test organs. In preparations sensitive to eserine, the anticholinesterase actions of the drugs competed with their anti-acetylcholine actions, so that either potentiation or block of responses to acetylcholine and to cholinergic nerve stimulation occurred with different concentrations. The responses of the toad bladder to acetylcholine were not potentiated by eserine. This enabled the antagonism of acetylcholine by the anti-adrenergic drugs to be estimated without interference from their anticholinesterase activity. When blocking activity was assessed on guinea-pig rectum previously treated with dyflos, the results were qualitatively similar to those on the toad bladder. Phenoxybenzamine often completely blocks responses both to added acetylcholine and to cholinergic nerve stimulation in concentrations less than those required to block adrenergic nerves. Guanethidine and piperoxan also show strong cholinergic blocking activity. Bretylium, yohimbine, tolazoline and phentolamine were less potent. However, in concentrations required to block the effect on the vas deferens of hypogastric nerve stimulation, these drugs at least halved the effects of acetylcholine and often of cholinergic nerve stimulation. It is concluded that these adrenergic blocking agents cannot be used to distinguish conclusively between adrenergic and cholinergic nerves. For reliable analysis of autonomic

  20. Evidence for the role of lipid rafts and sphingomyelin in Ca2+-gating of Transient Receptor Potential channels in trigeminal sensory neurons and peripheral nerve terminals.

    PubMed

    Sághy, Éva; Szőke, Éva; Payrits, Maja; Helyes, Zsuzsanna; Börzsei, Rita; Erostyák, János; Jánosi, Tibor Zoltán; Sétáló, György; Szolcsányi, János

    2015-10-01

    Transient Receptor Potential (TRP) cation channels, such as TRP Vanilloid 1 and TRP Ankyrin repeat domain 1 (TRPV1 and TRPA1) are nocisensors playing important role to signal pain. Two "melastatin" TRP receptors, like TRPM8 and TRPM3 are also expressed in a subgroup of primary sensory neurons. These channels serve as thermosensors with unique thermal sensitivity ranges and are activated also by several exogenous and endogenous chemical ligands inducing conformational changes from various allosteric ("multisteric") sites. We analysed the role of plasma membrane microdomains of lipid rafts on isolated trigeminal (TRG) neurons and TRPV1-expressing CHO cell line by measuring agonist-induced Ca2+ transients with ratiometric technique. Stimulation-evoked calcitonin gene related peptide (CGRP) release from sensory nerve endings of the isolated rat trachea by radioimmunoassay was also measured. Lipid rafts were disrupted by cleaving sphingomyelin (SM) with sphingomyelinase (SMase), cholesterol depletion with methyl β-cyclodextrin (MCD) and ganglioside breakdown with myriocin. It has been revealed that intracellular Ca2+ increase responses evoked by the TRPV1 agonist capsaicin, the TRPA1 agonsits allyl isothiocyanate (AITC) and formaldehyde as well as the TRPM8 activator icilin were inhibited after SMase, MCD and myriocin incubation but the response to the TRPM3 agonist pregnenolon sulphate was not altered. Extracellular SMase treatment did not influence the thapsigargin-evoked Ca2+-release from intracellular stores. Besides the cell bodies, SMase also inhibited capsaicin- or AITC-evoked CGRP release from peripheral sensory nerve terminals, this provides the first evidence for the importance of lipid raft integrity in TRPV1 and TRPA1 gating on capsaicin-sensitive nerve terminals. SM metabolites, ceramide and sphingosine, did not influence TRPA1 and TRPV1 activation on TRG neurons, TRPV1-expressing CHO cell line, and nerve terminals. We suggest, that the hydrophobic

  1. Epidermal adrenergic signaling contributes to inflammation and pain sensitization in a rat model of complex regional pain syndrome.

    PubMed

    Li, Wenwu; Shi, Xiaoyou; Wang, Liping; Guo, Tianzhi; Wei, Tzuping; Cheng, Kejun; Rice, Kenner C; Kingery, Wade S; Clark, J David

    2013-08-01

    In many patients, the sympathetic nervous system supports pain and other features of complex regional pain syndrome (CRPS). Accumulating evidence suggests that interleukin (IL)-6 also plays a role in CRPS, and that catecholamines stimulate production of IL-6 in several tissues. We hypothesized that norepinephrine acting through specific adrenergic receptors expressed on keratinocytes stimulates the production of IL-6 and leads to nociceptive sensitization in a rat tibial fracture/cast model of CRPS. Our approach involved catecholamine depletion using 6-hydroxydopamine or, alternatively, guanethidine, to explore sympathetic contributions. Both agents substantially reduced nociceptive sensitization and selectively reduced the production of IL-6 in skin. Antagonism of IL-6 signaling using TB-2-081 also reduced sensitization in this model. Experiments using a rat keratinocyte cell line demonstrated relatively high levels of β2-adrenergic receptor (β2-AR) expression. Stimulation of this receptor greatly enhanced IL-6 expression when compared to the expression of IL-1β, tumor necrosis factor (TNF)-α, or nerve growth factor. Stimulation of the cells also promoted phosphorylation of the mitogen-activated protein kinases P38, extracellular signal-regulated kinase, and c-Jun amino-terminal kinase. Based on these in vitro results, we returned to animal testing and observed that the selective β2-AR antagonist butoxamine reduced nociceptive sensitization in the CRPS model, and that local injection of the selective β2-AR agonist terbutaline resulted in mechanical allodynia and the production of IL-6 in the cells of the skin. No increases in IL-1β, TNF-α, or nerve growth factor levels were seen, however. These data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates β2-ARs expressed on epidermal keratinocytes, resulting in local IL-6 production, and ultimately, pain sensitization.

  2. Gulf War illnesses are autoimmune illnesses caused by increased activity of the p38/MAPK pathway in CD4+ immune system cells, which was caused by nerve agent prophylaxis and adrenergic load.

    PubMed

    Moss, J I

    2013-12-01

    Sodium chloride intake might increase the risk for the development of autoimmune diseases by increasing the activity of the p38/MAPK pathway in CD4+ cells thereby producing pathogenic TH17 cells which are inflammatory. Two factors (muscarinic and beta adrenergic stimulation), already shown to potentiate each other's toxic effects in whole mice, and have combined amplified sub lethal effects on mouse T cells, can have the same effect on CD4+ signaling pathways as sodium chloride. Sick 1991 Gulf War veterans express elevated Th17 cytokine activity, and therefore may have autoimmune illnesses caused directly by the above mentioned exposures.

  3. Neurotoxic potential of lunar and martian dust: influence on em, proton gradient, active transport, and binding of glutamate in rat brain nerve terminals.

    PubMed

    Krisanova, Natalia; Kasatkina, Ludmila; Sivko, Roman; Borysov, Arseniy; Nazarova, Anastasiya; Slenzka, Klaus; Borisova, Tatiana

    2013-08-01

    The harmful effects of lunar dust (LD) on directly exposed tissues are documented in the literature, whereas researchers are only recently beginning to consider its effects on indirectly exposed tissues. During inhalation, nano-/microsized particles are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of LD and martian dust (MD) has not yet been assessed. Glutamate is the main excitatory neurotransmitter involved in most aspects of normal brain function, whereas disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The research was focused on the analysis of the effects of LD/MD simulants (JSC-1a/JSC, derived from volcanic ash) on the key characteristics of glutamatergic neurotransmission. The average size of LD and MD particles (even minor fractions) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled l-[(14)C]glutamate, it was shown that there is an increase in l-[(14)C]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Na(+)] media and at low temperature in the presence of LD. MD caused significantly lesser changes under the same conditions, whereas nanoparticles of magnetite had no effect at all. Fluorimetric experiments with potential-sensitive dye rhodamine 6G and pH-sensitive dye acridine orange showed that the potential of the plasma membrane of the nerve terminals and acidification of synaptic vesicles were not altered by LD/MD (and nanoparticles of magnetite). Thus, the unique effect of LD to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on extracellular glutamate homeostasis in the central nervous system and cause alterations in the ambient level of glutamate, which is extremely important for proper synaptic transmission. During a long-term mission, a combination of constant irritation due

  4. Neurotoxic potential of lunar and martian dust: influence on em, proton gradient, active transport, and binding of glutamate in rat brain nerve terminals.

    PubMed

    Krisanova, Natalia; Kasatkina, Ludmila; Sivko, Roman; Borysov, Arseniy; Nazarova, Anastasiya; Slenzka, Klaus; Borisova, Tatiana

    2013-08-01

    The harmful effects of lunar dust (LD) on directly exposed tissues are documented in the literature, whereas researchers are only recently beginning to consider its effects on indirectly exposed tissues. During inhalation, nano-/microsized particles are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of LD and martian dust (MD) has not yet been assessed. Glutamate is the main excitatory neurotransmitter involved in most aspects of normal brain function, whereas disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The research was focused on the analysis of the effects of LD/MD simulants (JSC-1a/JSC, derived from volcanic ash) on the key characteristics of glutamatergic neurotransmission. The average size of LD and MD particles (even minor fractions) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled l-[(14)C]glutamate, it was shown that there is an increase in l-[(14)C]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Na(+)] media and at low temperature in the presence of LD. MD caused significantly lesser changes under the same conditions, whereas nanoparticles of magnetite had no effect at all. Fluorimetric experiments with potential-sensitive dye rhodamine 6G and pH-sensitive dye acridine orange showed that the potential of the plasma membrane of the nerve terminals and acidification of synaptic vesicles were not altered by LD/MD (and nanoparticles of magnetite). Thus, the unique effect of LD to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on extracellular glutamate homeostasis in the central nervous system and cause alterations in the ambient level of glutamate, which is extremely important for proper synaptic transmission. During a long-term mission, a combination of constant irritation due

  5. Mechanisms underlying presynaptic Ca2+ transient and vesicular glutamate release at a CNS nerve terminal during in vitro ischaemia

    PubMed Central

    Lee, Seul Yi; Kim, Jun Hee

    2015-01-01

    Key points Here we demonstrate presynaptic responses and mechanisms of increased vesicular glutamate release during in vitro ischaemia in the calyx of Held terminal, an experimentally accessible presynaptic terminal in the CNS. The ischaemia-induced increase in presynaptic Ca2+ was mediated by both Ca2+ influx and Ca2+-induced Ca2+ release from intracellular stores. The reverse operation of the plasma membrane Na+/Ca2+ exchanger (NCX) plays a key role in Ca2+ influx for triggering Ca2+ release from intracellular stores at presynaptic terminals during in vitro ischaemia. Ca2+ uptake via NCX underlies the ischaemia-induced Ca2+ rise and the consequent increase in vesicular glutamate release from presynaptic terminals in the early phase of brain ischaemia. Abstract An early consequence of brain ischaemia is an increase in vesicular glutamate release from presynaptic terminals. However, the mechanisms of this increased glutamate release are not fully understood. Here we studied presynaptic responses and mechanisms of increased glutamate release during in vitro ischaemia, using pre- and postsynaptic whole-cell recordings and presynaptic Ca2+ imaging at the calyx of Held synapse in rat brainstem slices. Consistent with results from other brain regions, in vitro ischaemia significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) without affecting their amplitude, suggesting that ischaemia enhances vesicular glutamate release from presynaptic terminals. We found that ischaemia-induced vesicular glutamate release was dependent on a rise in basal Ca2+ at presynaptic terminals, which resulted from extracellular Ca2+ influx and Ca2+ release from intracellular stores. During early ischaemia, increased Ca2+ influx into presynaptic terminals was due to reverse operation of the plasma membrane Na+/Ca2+ exchanger (NCX) rather than presynaptic depolarization or voltage-activated Ca2+ currents. KB-R7943, an inhibitor of NCX, prevented the

  6. Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: radiochemical and real-time video-microscopy studies.

    PubMed

    Correia-de-Sá, Paulo; Noronha-Matos, José B; Timóteo, Maria A; Ferreirinha, Fátima; Marques, Patrícia; Soares, Andreimar M; Carvalho, Cicilia; Cavalcante, Walter L G; Gallacci, Márcia

    2013-01-01

    Understanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA(2) homologue from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 μM) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [(3)H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. PMID:23142504

  7. Large conductance calcium-activated potassium channels: their expression and modulation of glutamate release from nerve terminals isolated from rat trigeminal caudal nucleus and cerebral cortex.

    PubMed

    Samengo, Irene; Currò, Diego; Barrese, Vincenzo; Taglialatela, Maurizio; Martire, Maria

    2014-05-01

    Large conductance, calcium-activated potassium channels [big potassium (BK) channel] consist of a tetramer of pore-forming α-subunit and distinct accessory β-subunits (β1-4) that modify the channel's properties. In this study, we analyzed the effects of BK channel activators and blockers on glutamate and γ-aminobutyric acid (GABA) release from synaptosomes isolated from the cerebral cortices or trigeminal caudal nuclei (TCN) of rats. Real-time polymerase chain reaction was used to characterize BK channel α and β(1-4) subunit expression in the cortex and in the trigeminal ganglia (TG), whose neurons project primary terminal afferents into the TCN. Immunocytochemistry was used to localize these subunits on cortical and TCN synaptosomes. The BK channels regulating [(3)H]D-aspartate release from primary afferent nerve terminals projecting into the TCN displayed limited sensitivity to iberiotoxin, whereas those expressed on cortical synaptosomes were highly sensitive to this toxin. BK channels did not appear to be present on GABAergic nerve terminals from the TCN since [(3)H]-γ-aminobutyric acid release in this model was unaffected by BK channel activators or blockers. Gene expression studies revealed expression levels of the α subunit in the TG that were only 31.2 ± 2.1% of those found in cortical tissues. The β4 subunit was the accessory subunit expressed most abundantly in both the cortex and TG. Levels of β1 and β2 were low in both these areas although β2 expression in the TG was higher than that found in the cortex. Immunocytochemistry experiments showed that co-localization of α and β4 subunits (the accessory subunit most abundantly expressed in both brain areas) was more common in TCN synaptosomes than in cortical synaptosomes. On the basis of these findings, it is reasonable to hypothesize that BK channels expressed on glutamatergic terminals in the TCN and cortex have distinct pharmacological profiles, which probably reflect different α and

  8. Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals.

    PubMed

    tom Dieck, S; Sanmartí-Vila, L; Langnaese, K; Richter, K; Kindler, S; Soyke, A; Wex, H; Smalla, K H; Kämpf, U; Fränzer, J T; Stumm, M; Garner, C C; Gundelfinger, E D

    1998-07-27

    The molecular architecture of the cytomatrix of presynaptic nerve terminals is poorly understood. Here we show that Bassoon, a novel protein of >400,000 Mr, is a new component of the presynaptic cytoskeleton. The murine bassoon gene maps to chromosome 9F. A comparison with the corresponding rat cDNA identified 10 exons within its protein-coding region. The Bassoon protein is predicted to contain two double-zinc fingers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, respectively). In some human proteins, e.g., Huntingtin, abnormal amplification of such poly-glutamine regions causes late-onset neurodegeneration. Bassoon is highly enriched in synaptic protein preparations. In cultured hippocampal neurons, Bassoon colocalizes with the synaptic vesicle protein synaptophysin and Piccolo, a presynaptic cytomatrix component. At the ultrastructural level, Bassoon is detected in axon terminals of hippocampal neurons where it is highly concentrated in the vicinity of the active zone. Immunogold labeling of synaptosomes revealed that Bassoon is associated with material interspersed between clear synaptic vesicles, and biochemical studies suggest a tight association with cytoskeletal structures. These data indicate that Bassoon is a strong candidate to be involved in cytomatrix organization at the site of neurotransmitter release.

  9. Autonomic innervation of the urogenital system: adrenergic and cholinergic elements.

    PubMed

    McConnell, J; Benson, G S; Wood, J G

    1982-01-01

    The major organs of the male urogenital (UG) system have been examined in various mammals, including man, using light and electron microscopic (EM) histochemical methods. For the light microscopic study, the urinary bladder, the vas deferens and the penis (corpora cavernosa and corpus spongiosum) were studied in the rat, cat, dog, monkey and man using a glyoxylic acid (GA) method modified for peripheral adrenergic nerve fibers, and a thiocholine method for acetylcholinesterase (AChE). Fine structural analysis was done on the vasa of rat, cat, monkey and man, and on the bladder and penis of cat, dog, monkey and man. Tissue was fixed in glutaraldehyde (GMO) as a control or in glutaraldehyde-dichromate (GDC) for the specific localization of norepinephrine (NE). All organs studied demonstrated numerous adrenergic nerve fibers throughout the muscular layers, in the connective tissue, and in the adventitia of most blood vessels. These fibers had a brilliant fluorescence when visualized with the GA method, and demonstrated many varicosities with small (400-600 A) and/or large (800-1200 A) granular vesicles in both control and GDC-fixed tissue examined with the EM. Evaluation of the vesicles with the analytical electron microscope (AEM) verified that those in the GDC-fixed tissue were chrome-positive, and, therefore, NE-containing. In the vas and penis, acetylcholinesterase(AChE)-positive nerve fibers were encountered less frequently at the light microscopic level than adrenergic fibers, and few typical cholinergic varicosities were seen in these organs with the EM. In the bladder, cholinergic nerves were seen with about the same frequency as adrenergic fibers in both light microscopic and EM preparations. Also observed frequently in each of the viscera were varicosities with large to very large (800-2000 A) granular vesicles of the kind presently hypothesized to be peptidergic or purinergic. Few varicosities of the type considered sensory, with large (800-1200 A) clear

  10. [Adrenergic receptors of blood platelets].

    PubMed

    Lanza, F; Cazenave, J P

    1987-01-01

    Blood platelets possess adrenergic receptors and are stimulated by adrenaline in the circulation. This review summarizes the state of knowledge of the pharmacology of adrenergic receptors and the biochemical mechanisms of platelet activation by adrenaline in various physiological and pathological conditions. PMID:2837727

  11. P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminals in an in vitro intra-arterially perfused rat tongue preparation.

    PubMed

    Rong, W; Burnstock, G; Spyer, K M

    2000-05-01

    A novel in vitro intra-arterially perfused adult rat tongue-nerve preparation was used to explore the possible actions of P2X purinoceptor agonists (ATP and alpha,beta-methylene ATP (alpha, beta-meATP)) on sensory nerve terminals innervating the rat tongue. We made whole-nerve recordings of the trigeminal branch of the lingual nerve (LN), which conducts general sensory information (pain, temperature, touch, etc.), and the chorda tympani (CT), which conducts taste information. Changes in LN and CT activity following intra-arterial application of P2X agonists were compared. In seven preparations, bolus close-arterial injection of ATP (30-3000 microM, 0.1 ml) or alpha,beta-meATP (10-300 microM, 0.1 ml) induced a rapid (< 1 s after injection), dose-related increase in LN activity that decayed within a few seconds. The minimal concentration of ATP (100 microM) required to elicit a response was about 10-fold higher than that of alpha,beta-meATP (10 microM). Bolus injection of ATP or alpha,beta-meATP induced a moderate decrease in firing frequency in three of seven CT preparations. LN responses to P2X agonists showed signs of rapid desensitisation with the peak frequency of discharge being smaller when the agonists were applied at short intervals. Suramin (200 microM) or PPADS (200 microM) applied by intra-arterial perfusion each antagonised the rapid increase in LN activity following application of alpha,beta-meATP (100 microM). Capsaicin (10 microM, 0.1 ml, n = 5 preparations) was injected intra-arterially to desensitise nociceptive fibres. This was found to block (n = 2) or greatly reduce (n = 3) the excitatory effects of alpha,beta-meATP (100 microM, 0.1 ml) on LN activity, implying that only capsaicin-sensitive nociceptive fibres in LN were responsive to P2X agonists. In contrast to the consistent excitatory responses in LN activity following fast application of P2X agonists as bolus, a variable and moderate change in discharge rate of LN and no change in CT activity

  12. beta. -Adrenergic stimulation of brown adipocyte proliferation

    SciTech Connect

    Geloeen, A.; Collet, A.J.; Guay, G.; Bukowiecki, L.J. Laboratoire de Thermoregulation et Metabolisme Energetique, Lyon )

    1988-01-01

    The mechanisms of brown adipose tissue (BAT) growth were studied by quantitative photonic radioautography using tritiated thymidine to follow mitotic activity. To identify the nature of the adrenergic pathways mediating brown adipocyte proliferation and differentiation, the effects of cold exposure (4 days at 4{degree}C) on BAT growth were compared with those induced by treating rats at 25{degree}C with norepinephrine (a mixed agonist), isoproterenol (a {beta}-agonist), and phenylephrine (an {alpha}-agonist). Norepinephrine mimicked the effects of cold exposure, not only on the mitotic activity, but also on the distribution of the labeling among the various cellular types. Isoproterenol entirely reproduced the effects of norepinephrine both on the labeling index and on the cellular type labeling frequency. These results demonstrate that norepinephrine triggers a coordinated proliferation of brown adipocytes and endothelial cells in warm-exposed rats that is similar to that observed after cold exposure. They also suggest that cold exposure stimulates BAT growth by increasing the release of norepinephrine from sympathetic nerves and that the neurohormone activates mitoses in BAT precursor cells via {beta}-adrenergic pathways.

  13. The small conductance Ca2+-activated K+ channel SK3 is localized in nerve terminals of excitatory synapses of cultured mouse hippocampal neurons.

    PubMed

    Obermair, Gerald J; Kaufmann, Walter A; Knaus, Hans-Günther; Flucher, Bernhard E

    2003-02-01

    In the central nervous system small conductance Ca2+-activated K+ (SK) channels are important for generating the medium/slow afterhyperpolarization seen after single or trains of action potentials. Three SK channel isoforms (SK1,-2,-3) are differentially distributed throughout the brain, but little is known about their specific expression in particular neuronal compartments. In the hippocampus SK3 was found in the neuropil, predominantly in the terminal field of the mossy fibres and in fine varicose fibres, but excluded from the pyramidal and granule cell layers. Because this expression pattern suggested a presynaptic localization, we examined the subcellular distribution of SK3 in cultured hippocampal neurons using high-resolution immunofluorescence analysis. SK3 was localized in a punctate, synaptic pattern. The SK3 clusters were precisely colocalized with the presynaptic marker synapsin and at close range (0.4-0.5 microm) from NMDA-receptors and PSD-95. This arrangement is consistent with a localization of SK3 in the presynaptic nerve terminal, but not restricted to the synaptic membrane proper. In agreement with the increasing expression of SK3 during early postnatal development in vivo, the fraction of synapses containing SK3 increased from 14% to 57% over a six-week culture period. SK3-containing synapses were equally observed on spiny, glutamatergic and smooth GABAergic neurons. In contrast to its close association with NMDA-receptors and PSD-95, SK3 was rarely associated with GABAA-receptor clusters. Thus, SK3 is a presynaptic channel in excitatory hippocampal synapses, with no preference for glutamatergic or GABAergic postsynaptic neurons, and is probably involved in regulating neurotransmitter release.

  14. A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration

    PubMed Central

    Ferris, Mark J; Calipari, Erin S; Rose, Jamie H; Siciliano, Cody A; Sun, Haiguo; Chen, Rong; Jones, Sara R

    2015-01-01

    There are ∼1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans. It is hypothesized that amphetamine acts as a replacement therapy for cocaine through elevation of extracellular dopamine levels. Using voltammetry in brain slices, we tested the ability of a single amphetamine infusion in vivo to modulate dopamine release, uptake kinetics, and cocaine potency in cocaine-naive animals and after a history of cocaine self-administration (1.5 mg/kg/infusion, fixed-ratio 1, 40 injections/day × 5 days). Dopamine kinetics were measured 1 and 24 h after amphetamine infusion (0.56 mg/kg, i.v.). Following cocaine self-administration, dopamine release, maximal rate of uptake (Vmax), and membrane-associated dopamine transporter (DAT) levels were reduced, and the DAT was less sensitive to cocaine. A single amphetamine infusion reduced Vmax and membrane DAT levels in cocaine-naive animals, but fully restored all aspects of dopamine terminal function in cocaine self-administering animals. Here, for the first time, we demonstrate pharmacologically induced, immediate rescue of deficits in dopamine nerve-terminal function in animals with a history of high-dose cocaine self-administration. This observation supports the notion that the DAT expression and function can be modulated on a rapid timescale and also suggests that the pharmacotherapeutic actions of amphetamine for cocaine addiction go beyond that of replacement therapy. PMID:25689882

  15. A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration.

    PubMed

    Ferris, Mark J; Calipari, Erin S; Rose, Jamie H; Siciliano, Cody A; Sun, Haiguo; Chen, Rong; Jones, Sara R

    2015-07-01

    There are ∼ 1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans. It is hypothesized that amphetamine acts as a replacement therapy for cocaine through elevation of extracellular dopamine levels. Using voltammetry in brain slices, we tested the ability of a single amphetamine infusion in vivo to modulate dopamine release, uptake kinetics, and cocaine potency in cocaine-naive animals and after a history of cocaine self-administration (1.5 mg/kg/infusion, fixed-ratio 1, 40 injections/day × 5 days). Dopamine kinetics were measured 1 and 24 h after amphetamine infusion (0.56 mg/kg, i.v.). Following cocaine self-administration, dopamine release, maximal rate of uptake (Vmax), and membrane-associated dopamine transporter (DAT) levels were reduced, and the DAT was less sensitive to cocaine. A single amphetamine infusion reduced Vmax and membrane DAT levels in cocaine-naive animals, but fully restored all aspects of dopamine terminal function in cocaine self-administering animals. Here, for the first time, we demonstrate pharmacologically induced, immediate rescue of deficits in dopamine nerve-terminal function in animals with a history of high-dose cocaine self-administration. This observation supports the notion that the DAT expression and function can be modulated on a rapid timescale and also suggests that the pharmacotherapeutic actions of amphetamine for cocaine addiction go beyond that of replacement therapy. PMID:25689882

  16. Effect of the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon on the glutamate release from rat brain nerve terminals under altered gravity conditions.

    NASA Astrophysics Data System (ADS)

    Borisova, T.; Krisanova, N.

    L-glutamate acts within the mammalian central nervous system as the predominant excitatory neurotransmitter and as a potent neurotoxin The balance between these physiological and pathological actions of glutamate is thought to be kept in check by the rapid removal of the neurotransmitter from the synaptic cleft The majority of uptake is mediated by the high-affinity Na -dependent glutamate transporters Depolarization leads to stimulation of glutamate efflux mediated by reversal of the high-affinity glutamate transporters The effects of the protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon FCCP on the glutamate release from isolated nerve terminals rat brain synaptosomes were investigated in control and after centrifuge-induced hypergravity rats were rotated in a long-arm centrifuge at ten-G during one-hour period The treatment of synaptosomes with 1 mu M FCCP during 11 min resulted in the increase in L- 14 C glutamate release by 23 0 pm 2 3 of total accumulated synaptosomal label in control animals and 24 0 pm 2 3 animals subjected to hypergravity FCCP evoked release of L- 14 C glutamate from synaptosomes was not altered in animals exposed to hypergravity as compared to control Glutamate transport is of electrogenic nature and thus depends on the membrane potential The high-KCl stimulated L- 14 C glutamate release in Ca 2 -free media occurred due to reversal of the glutamate transporters Carrier --mediated release of L- 14 C glutamate 6 min slightly increased as a result of

  17. Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals

    PubMed Central

    Lu, Cheng Wei; Lin, Tzu Yu; Huang, Shu Kuei; Wang, Su Jane

    2016-01-01

    The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca2+-dependent, but not Ca2+-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner. Echinacoside also reduced the 4-aminopyridine-evoked increase in cytoplasmic free Ca2+ concentration but did not alter the synaptosomal membrane potential. The inhibitory effect of echinacoside on 4-aminopyridine-evoked glutamate release was prevented by ω-conotoxin MVIIC, a wide-spectrum blocker of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but was insensitive to the intracellular Ca2+ release-inhibitors dantrolene and 7-chloro-5-(2-chloropheny)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157). Furthermore, echinacoside decreased the 4-aminopyridine-induced phosphorylation of protein kinase C, and protein kinase C inhibitors abolished the effect of echinacoside on glutamate release. According to these results, we suggest that the inhibitory effect of echinacoside on evoked glutamate release is associated with reduced voltage-dependent Ca2+ entry and subsequent suppression of protein kinase C activity. PMID:27347934

  18. Adrenergic receptor subtypes in the cerebral circulation of newborn piglets

    SciTech Connect

    Wagerle, L.C.; Delivoria-Papadopoulos, M.

    1987-06-01

    The purpose of this study was to identify the ..cap alpha..-adrenergic receptor subtype mediating cerebral vasoconstriction during sympathetic nerve stimulation in the newborn piglet. The effect of ..cap alpha../sub 1/- and ..cap alpha../sub 2/-antagonists prazosin and yohimbine on the cerebrovascular response to unilateral electrical stimulation (15 Hz, 15 V) of the superior cervical sympathetic trunk was studied in 25 newborn piglets. Regional cerebral blood flow was measured with tracer microspheres. Sympathetic stimulation decreased blood flow to the ipsilateral cerebrum hippocampus, choroid plexus, and masseter muscle. ..cap alpha../sub 1/-Adrenergic receptor blockade with prazosin inhibited the sympathetic vasoconstriction in the cerebrum, hippocampus, and masseter muscle and abolished it in the choroid plexus. ..cap alpha../sub s/-Adrenergic receptor blockade with yohimbine had no effect. Following the higher dose of yohimbine, however, blood flow to all brain regions was increased by approximately two-fold, possibly due to enhanced cerebral metabolism. These data demonstrate that vascular ..cap alpha../sub 1/-adrenergic receptors mediate vasoconstriction to neuroadrenergic stimulation in cerebral resistance vessels in the newborn piglet.

  19. Kinetics, Ca2+ dependence, and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor nerve terminals

    NASA Technical Reports Server (NTRS)

    Chen, B. M.; Grinnell, A. D.

    1997-01-01

    Neurotransmitter release from frog motor nerve terminals is strongly modulated by change in muscle length. Over the physiological range, there is an approximately 10% increase in spontaneous and evoked release per 1% muscle stretch. Because many muscle fibers do not receive suprathreshold synaptic inputs at rest length, this stretch-induced enhancement of release constitutes a strong peripheral amplifier of the spinal stretch reflex. The stretch modulation of release is inhibited by peptides that block integrin binding of natural ligands. The modulation varies linearly with length, with a delay of no more than approximately 1-2 msec and is maintained constant at the new length. Moreover, the stretch modulation persists in a zero Ca2+ Ringer and, hence, is not dependent on Ca2+ influx through stretch activated channels. Eliminating transmembrane Ca2+ gradients and buffering intraterminal Ca2+ to approximately normal resting levels does not eliminate the modulation, suggesting that it is not the result of release of Ca2+ from internal stores. Finally, changes in temperature have no detectable effect on the kinetics of stretch-induced changes in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We conclude, therefore, that stretch does not act via second messenger pathways or a chemical modification of molecules involved in the release pathway. Instead, there is direct mechanical modulation of release. We postulate that tension on integrins in the presynaptic membrane is transduced mechanically into changes in the position or conformation of one or more molecules involved in neurotransmitter release, altering sensitivity to Ca2+ or the equilibrium for a critical reaction leading to vesicle fusion.

  20. Acquisition of Spontaneous Electrical Activity During Embryonic Development of Gonadotropin-Releasing Hormone-3 Neurons Located in the Terminal Nerve of Transgenic Zebrafish (Danio rerio)

    PubMed Central

    Ramakrishnan, Siddharth; Lee, Wenjau; Navarre, Sammy; Kozlowski, David J.; Wayne, Nancy L.

    2010-01-01

    There are multiple populations of gonadotropin releasing hormone (GnRH) neurons that have distinct physiological and behavioral functions. Teleost fish have a population of GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb that is thought to play a neuromodulatory role in multiple physiological systems, including olfactory, visual, and reproductive. We used transgenic zebrafish in which the GnRH3 promoter drives expression of a green fluorescent protein to identify GnRH3 neurons during development in live embryos. Unlike with hypophysiotropic GnRH neurons of zebrafish, TN-GnRH3 neurons are of neural crest origin and are one of the first populations of GnRH neurons to develop in the early embryo. Using a combination of optical imaging and electrophysiology, we showed that during the first three days post-fertilization, TN-GnRH3 neurons increase in number, extend neural projections, move in association with tissue expansion, and acquire an adult-pattern of spontaneous action potential firing. Early during development, about half of the neurons were quiescent/non-firing. Later, at three days post-fertilization, there was an increase in the proportion of neurons showing action potential firing and an increase in the number of neurons that showed an adult-like tonic or beating pattern of action potential firing with a firing frequency similar to that seen in adult TN-GnRH3 neurons. This study represents the first neurophysiological investigation of developing GnRH neurons in live embryos -- an important advance in understanding their potential non-reproductive roles during embryogenesis. PMID:20515692

  1. Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle

    PubMed Central

    Ajijola, Olujimi A.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; Benharash, Peyman; Hadaya, Joseph; Lux, Robert L.; Mahajan, Aman

    2013-01-01

    Increased cardiac sympathetic activation worsens dispersion of repolarization and is proarrhythmic. The functional differences between intrinsic nerve stimulation and adrenergic receptor activation remain incompletely understood. This study was undertaken to determine the functional differences between efferent cardiac sympathetic nerve stimulation and direct adrenergic receptor activation in porcine ventricles. Female Yorkshire pigs (n = 13) underwent surgical exposure of the heart and stellate ganglia. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent bilateral sympathetic stimulation (BSS) (n = 8) or norepinephrine (NE) administration (n = 5). Activation recovery intervals (ARIs) were measured at each electrode before and during BSS or NE. The degree of ARI shortening during BSS or NE administration was used as a measure of functional nerve or adrenergic receptor density. During BSS, ARI shortening was nonuniform across the epicardium (F value 9.62, P = 0.003), with ARI shortening greatest in the mid-basal lateral right ventricle and least in the midposterior left ventricle (LV) (mean normalized values: 0.9 ± 0.08 vs. 0.56 ± 0.08; P = 0.03). NE administration resulted in greater ARI shortening in the LV apex than basal segments [0.91 ± 0.04 vs. 0.63 ± 0.05 (averaged basal segments); P = 0.003]. Dispersion of ARIs increased in 50% and 60% of the subjects undergoing BSS and NE, respectively, but decreased in the others. There is nonuniform response to cardiac sympathetic activation of both porcine ventricles, which is not fully explained by adrenergic receptor density. Different pools of adrenergic receptors may mediate the cardiac electrophysiological effects of efferent sympathetic nerve activity and circulating catecholamines. PMID:23241324

  2. Manipulation of isolated brain nerve terminals by an external magnetic field using D-mannose-coated γ-Fe2O3 nano-sized particles and assessment of their effects on glutamate transport

    PubMed Central

    Krisanova, Natalia; Borуsov, Arsenii; Sivko, Roman; Ostapchenko, Ludmila; Babic, Michal; Horak, Daniel

    2014-01-01

    Summary The manipulation of brain nerve terminals by an external magnetic field promises breakthroughs in nano-neurotechnology. D-Mannose-coated superparamagnetic nanoparticles were synthesized by coprecipitation of Fe(II) and Fe(III) salts followed by oxidation with sodium hypochlorite and addition of D-mannose. Effects of D-mannose-coated superparamagnetic maghemite (γ-Fe2O3) nanoparticles on key characteristics of the glutamatergic neurotransmission were analysed. Using radiolabeled L-[14C]glutamate, it was shown that D-mannose-coated γ-Fe2O3 nanoparticles did not affect high-affinity Na+-dependent uptake, tonic release and the extracellular level of L-[14C]glutamate in isolated rat brain nerve terminals (synaptosomes). Also, the membrane potential of synaptosomes and acidification of synaptic vesicles was not changed as a result of the application of D-mannose-coated γ-Fe2O3 nanoparticles. This was demonstrated with the potential-sensitive fluorescent dye rhodamine 6G and the pH-sensitive dye acridine orange. The study also focused on the analysis of the potential use of these nanoparticles for manipulation of nerve terminals by an external magnetic field. It was shown that more than 84.3 ± 5.0% of L-[14C]glutamate-loaded synaptosomes (1 mg of protein/mL) incubated for 5 min with D-mannose-coated γ-Fe2O3 nanoparticles (250 µg/mL) moved to an area, in which the magnet (250 mT, gradient 5.5 Т/m) was applied compared to 33.5 ± 3.0% of the control and 48.6 ± 3.0% of samples that were treated with uncoated nanoparticles. Therefore, isolated brain nerve terminals can be easily manipulated by an external magnetic field using D-mannose-coated γ-Fe2O3 nanoparticles, while the key characteristics of glutamatergic neurotransmission are not affected. In other words, functionally active synaptosomes labeled with D-mannose-coated γ-Fe2O3 nanoparticles were obtained. PMID:24991515

  3. The role of median nerve terminal latency index in the diagnosis of carpal tunnel syndrome in comparison with other electrodiagnostic parameters

    PubMed Central

    Vahdatpour, Babak; Khosrawi, Saeid; Chatraei, Maryam

    2016-01-01

    Background: Carpal tunnel syndrome (CTS) considers the most common compression neuropathy, which nerve conduction studies (NCSs) used for its detection routinely and universally. This study was performed to determine the value of the median TLI and other NCS variables and to investigate their sensitivity and specificity in the diagnosis of CTS. Materials and Methods: The study was carried out among 100 hands of healthy volunteers and 50 hands of patients who had a positive history of paresthesia and numbness in upper extremities. Information including age, gender, and result of sensory and motor nerve conduction velocity (MNCV), peak latency difference of median and ulnar nerves of fourth digit (M4-U4 peak latency difference), and TLI were recorded for analysis. Sensitivity and specificity of electro diagnostic parameters in the diagnosis of CTS was investigated. Results: Normal range of the median nerve TLI was 0.43 ± 0.077. There was no significant difference between two groups for MNCV means (P = 0. 45). Distal sensory latency and distal motor latency (DML) of median nerve and fourth digit median-ulnar peak latency differences (PM4-PU4) for CTS group was significantly higher (P < 0.001) and mean for sensory nerve conduction velocity was significantly higher in control group (P < 0.001). The most sensitive electrophysiological finding in CTS patients was median TLI (82%), but the most specific one was DML (98%). Conclusion: Although in early stages of CTS, we usually expect only abnormalities in the sensory studies, but TLI may better demonstrate the effect on median nerve motor fiber even in mild cases of CTS. PMID:27376049

  4. Neural Blockade Anaesthesia of the Mandibular Nerve and Its Terminal Branches: Rationale for Different Anaesthetic Techniques Including Their Advantages and Disadvantages

    PubMed Central

    Khoury, Jason; Townsend, Grant

    2011-01-01

    Anaesthesia of structures innervated by the mandibular nerve is necessary to provide adequate pain control when performing dental and localised surgical procedures. To date, numerous techniques have been described and, although many of these methods are not used routinely, there are some situations where their application may be indicated. Patient factors as well as anatomical variability of the mandibular nerve and associated structures dictate that no one technique can be universally applied with a 100% success rate. This fact has led to a proliferation of alternative techniques that have appeared in the literature. This selective review of the literature provides a brief description of the different techniques available to the clinician as well as the underlying anatomy which is fundamental to successfully anaesthetising the mandibular nerve. PMID:21716730

  5. Leutropin/beta-adrenergic receptor chimeras bind choriogonadotropin and adrenergic ligands but are not expressed at the cell surface.

    PubMed

    Moyle, W R; Bernard, M P; Myers, R V; Marko, O M; Strader, C D

    1991-06-15

    In some G-protein-coupled receptors (e.g. beta-adrenergic receptor (beta 2 AR)), the ligand-binding pocket is contained within the hydrophobic transmembrane domain. In others (e.g. luteinizing hormone receptor (LHR)), the relative roles of the extracellular N-terminal domain and the transmembrane region in hormone binding are unknown. To study the roles of these domains, we prepared vectors encoding the rat LHR N-terminal domain alone (L- -), the LHR N-terminal domain fused to the transmembrane and C-terminal domains of the vesicular stomatitis virus-G protein (LVV), the LHR N-terminal domain fused to the transmembrane and C-terminal domains of the hamster beta 2 AR (LAA), and the beta 2 AR N-terminal domain fused to the transmembrane and C-terminal domains of the rat LHR (ALL). Membrane preparations obtained from COS-7 cells expressing the beta 2 AR or LAA bound the beta-adrenergic antagonist 125I-cyanopindolol with equal affinity, confirming the observation that the beta 2 AR transmembrane domain forms the hormone-binding site. Membranes from COS-7 cells transfected with LHR bound 125I-human choriomic gonadotropin (hCG). However, membranes from LAA-, L(- -)-, and LVV-transfected cells had low capacity to bind 125I-hCG unless they were solubilized with Triton X-100. The affinity of the detergent-solubilized receptors for 125I-hCG was similar to that of the LHR. We were unable to detect binding of 125I-hCG to ALL in the presence or absence of detergent. These observations suggest that, whereas the transmembrane region of the beta 2 AR is sufficient to bind adrenergic ligands, the N-terminal region of the LHR is required for binding of hCG. Although the N terminus of the LHR is sufficient to bind hCG, both the N terminus and the transmembrane domains of the LHR are required for receptor expression on the cell surface.

  6. Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight

    NASA Technical Reports Server (NTRS)

    Meck, Janice V.; Waters, Wendy W.; Ziegler, Michael G.; deBlock, Heidi F.; Mills, Paul J.; Robertson, David; Huang, Paul L.

    2004-01-01

    Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1). significantly smaller pressor responses to phenylephrine both before and after flight; 2). significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3). significantly greater norepinephrine release with tyramine on landing day; and 4). significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.

  7. Ganglionic adrenergic action modulates ovarian steroids and nitric oxide in prepubertal rat.

    PubMed

    Delgado, Silvia Marcela; Casais, Marilina; Sosa, Zulema; Rastrilla, Ana María

    2006-08-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. The purpose of this work was to analyse the ganglionic adrenergic influence on the ovarian release of steroids and NO and the possible steroids/NO relationship. The experiments were carried out in the ex vivo coeliac ganglion-superior ovarian nerve (SON)-ovary system of prepubertal rats. The coeliac ganglion-SON-ovary system was incubated in Krebs Ringer-bicarbonate buffer in presence of adrenergic agents in the ganglionic compartment. The accumulation of progesterone, androstenedione, oestradiol and NO in the ovarian incubation liquid was measured. Norepinephrine in coeliac ganglion inhibited the liberation of progesterone and increased androstenedione, oestradiol and NO in ovary. The addition of alpha and beta adrenergic antagonists also showed different responses in the liberation of the substances mentioned before, which, from a physiological point of view, reveals the presence of adrenergic receptors in coeliac ganglion. In relation to propranolol, it does not revert the effect of noradrenaline on the liberation of progesterone, which leads us to think that it might also have a "per se" effect on the ganglion, responsible for the ovarian response observed for progesterone. Finally, we can conclude that the ganglionic adrenergic action via SON participates on the regulation of the prepubertal ovary in one of two ways: either increasing the NO, a gaseous neurotransmitter with cytostatic characteristics, to favour the immature follicles to remain dormant or increasing the liberation of androstenedione and oestradiol, the steroids necessary for the beginning of the near first estral cycle.

  8. Modification by choline of adrenergic transmission in rat mesenteric arteries

    PubMed Central

    Malik, K. U.; McGiff, J. C.

    1971-01-01

    1. The action of choline on the vasoconstrictor responses of the perfused mesenteric arteries of the rat to sympathetic nerve stimulation and to injected noradrenaline has been investigated. 2. The infusion of choline (500 μg/ml), for periods of 15 s, increased the response to sympathetic nerve stimulation, whereas the infusion of the same concentration for 20 min greatly reduced the response to nerve stimulation. Choline (up to 500 μg/ml), infused either for short or long periods, did not alter the response to injected noradrenaline. 3. The inhibitory action of choline on the response to nerve stimulation was abolished either by an increase in the calcium concentration from 1·8 to 5·4 mM or by simultaneous infusion of (+)-amphetamine or atropine. 4. The results suggest that choline in concentrations of 500 μg/ml has the same effect on adrenergic transmission in mesenteric arteries as acetylcholine at concentrations of 5 ng/ml. PMID:4339884

  9. Recent advances in research on nitrergic nerve-mediated vasodilatation.

    PubMed

    Toda, Noboru; Okamura, Tomio

    2015-06-01

    Cerebral vascular resistance and blood flow were widely considered to be regulated solely by tonic innervation of vasoconstrictor adrenergic nerves. However, pieces of evidence suggesting that parasympathetic nitrergic nerve activation elicits vasodilatation in dog and monkey cerebral arteries were found in 1990. Nitric oxide (NO) as a neurotransmitter liberated from parasympathetic postganglionic neurons decreases cerebral vascular tone and resistance and increases cerebral blood flow, which overcome vasoconstrictor responses to norepinephrine liberated from adrenergic nerves. Functional roles of nitrergic vasodilator nerves are found also in peripheral vasculature, including pulmonary, renal, mesenteric, hepatic, ocular, uterine, nasal, skeletal muscle, and cutaneous arteries and veins; however, adrenergic nerve-induced vasoconstriction is evidently greater than nitrergic vasodilatation in these vasculatures. In coronary arteries, neurogenic NO-mediated vasodilatation is not clearly noted; however, vasodilatation is induced by norepinephrine released from adrenergic nerves that activates β1-adrenoceptors. Impaired actions of NO liberated from the endothelium and nitrergic neurons are suggested to participate in cerebral hypoperfusion, leading to brain dysfunction, like that in Alzheimer's disease. Nitrergic neural dysfunction participates in impaired circulation in peripheral organs and tissues and also in systemic blood pressure increase. NO and vasodilator peptides, as sensory neuromediators, are involved in neurogenic vasodilatation in the skin. Functioning of nitrergic vasodilator nerves is evidenced not only in a variety of mammals, including humans and monkeys, but also in non-mammals. The present review article includes recent advances in research on the functional importance of nitrergic nerves concerning the control of cerebral blood flow, as well as other regions, and vascular resistance. Although information is still insufficient, the nitrergic nerve

  10. The nerves of the accessory pancreatic ducts of the common starling (Sturnus vulgaris): an ultrastructural and light microscopic study.

    PubMed Central

    McAllister, R M; Kendall, M D

    1984-01-01

    An ultrastructural and light microscopic study was undertaken to examine the nerves of the accessory pancreatic ducts of the starling (Sturnus vulgaris), previously noted (Vinnicombe, 1982) to have a particularly dense innervation. Large numbers of nerves were found in the ducts, predominantly in the lamina propria, and all contained exclusively unmyelinated axons. Probable neuron cell bodies were observed in the smooth muscle layer, but not in the lamina propria. Schwann cells invested all the axons, and these displayed terminal swellings in a 'synapse en passage' arrangement. The nerves of the lamina propria were most numerous in the region immediately beneath the epithelium and were present in the epithelial folds. One axon was observed to have penetrated the epithelial basal lamina and to lie between two epithelial cells. Examination of the terminal profiles and their contained synaptic vesicles showed the innervation to have probable pain afferent, cholinergic, adrenergic and perhaps peptidergic components. The results of this study were compared with reports on pancreatic duct innervation in other species, mostly as parts of wider studies on pancreatic innervation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6490527

  11. Beta Adrenergic Receptors in Keratinocytes

    PubMed Central

    Sivamani, Raja K.; Lam, Susanne T.; Isseroff, R. Rivkah

    2007-01-01

    Synopsis Beta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease. PMID:17903623

  12. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Update Date 6/1/2015 ...

  13. Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Yen, T. C.

    2002-01-01

    The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.

  14. Histamine H(3) receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries.

    PubMed

    Sun, Pengyuan; Takatori, Shingo; Jin, Xin; Koyama, Toshihiro; Tangsucharit, Panot; Li, Simin; Zamami, Yoshito; Kitamura, Yoshihisa; Kawasaki, Hiromu

    2011-03-25

    The rat mesenteric artery has been shown to be innervated by adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. The present study was designed to investigate the involvement of histamine H(3) receptors in the neurotransmission of perivascular adrenergic and CGRPergic nerves. The mesenteric vascular beds without an endothelium isolated from male Wistar rats were perfused with Krebs solution and perfusion pressure was measured. In preparations with resting tension, the selective H(3) receptor agonist (R)-α-methylhistamine (α-methylhistamine; 10-100nM) significantly reduced periarterial nerve stimulation (2-8Hz)-induced vasoconstriction and noradrenaline release in the perfusate without an effect on the vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0nmol). In preparations with active tone produced by methoxamine (2μM) and in the presence of guanethidine (5μM), the periarterial nerve stimulation (1, 2Hz)-induced vasodilator response was inhibited by α-methylhistamine (0.1-1μM) perfusion without affecting vasodilation induced by exogenously injected CGRP (5pmol). Clobenpropit (histamine H(3) receptor antagonist, 1μM) canceled the α-methylhistamine-induced decrease in the periarterial nerve stimulation-induced vasoconstriction and noradrenaline release and periarterial nerve stimulation-induced vasodilation. These results suggest that the stimulation of H(3) receptors located in rat perivascular nerves inhibits presynaptically the neurotransmission of not only adrenergic nerves, but also CGRP nerves, by decreasing neurotransmitters.

  15. A syntaxin 1, Galpha(o), and N-type calcium channel complex at a presynaptic nerve terminal: analysis by quantitative immunocolocalization.

    PubMed

    Li, Qi; Lau, Anthony; Morris, Terence J; Guo, Lin; Fordyce, Christopher B; Stanley, Elise F

    2004-04-21

    Presynaptic Ca(V)2.2 (N-type) calcium channels are subject to modulation by interaction with syntaxin 1 and by a syntaxin 1-sensitive Galpha(O) G-protein pathway. We used biochemical analysis of neuronal tissue lysates and a new quantitative test of colocalization by intensity correlation analysis at the giant calyx-type presynaptic terminal of the chick ciliary ganglion to explore the association of Ca(V)2.2 with syntaxin 1 and Galpha(O). Ca(V)2.2 could be localized by immunocytochemistry (antibody Ab571) in puncta on the release site aspect of the presynaptic terminal and close to synaptic vesicle clouds. Syntaxin 1 coimmunoprecipitated with Ca(V)2.2 from chick brain and chick ciliary ganglia and was widely distributed on the presynaptic terminal membrane. A fraction of the total syntaxin 1 colocalized with the Ca(V)2.2 puncta, whereas the bulk colocalized with MUNC18-1. Galpha(O,) whether in its trimeric or monomeric state, did not coimmunoprecipitate with Ca(V)2.2, MUNC18-1, or syntaxin 1. However, the G-protein exhibited a punctate staining on the calyx membrane with an intensity that varied in synchrony with that for both Ca channels and syntaxin 1 but only weakly with MUNC18-1. Thus, syntaxin 1 appears to be a component of two separate complexes at the presynaptic terminal, a minor one at the transmitter release site with Ca(V)2.2 and Galpha(O), as well as in large clusters remote from the release site with MUNC18-1. These syntaxin 1 protein complexes may play distinct roles in presynaptic biology.

  16. Preliminary crystallographic analysis of the N-terminal PDZ-like domain of periaxin, an abundant peripheral nerve protein linked to human neuropathies

    PubMed Central

    Han, Huijong; Kursula, Petri

    2013-01-01

    Periaxin (PRX) is an abundant protein in peripheral nerves and contains a predicted PDZ-like domain at its N-terminus. The large isoform, L-PRX, is required for the maintenance of myelin in the peripheral nervous system and its defects cause neurological disease. Here, the human periaxin PDZ-like domain was crystallized and X-ray diffraction data were collected to 2.85 Å resolution using synchrotron radiation. The crystal belonged to the primitive hexagonal space group P3121 or P3221, with unit-cell parameters a = b = 80.6, c = 81.0 Å, γ = 120° and either two or three molecules in the asymmetric unit. The structure of PRX will shed light on its poorly characterized function in the nervous system. PMID:23832213

  17. Beta-adrenergic-regulated phosphorylation of the skeletal muscle Ca(V)1.1 channel in the fight-or-flight response.

    PubMed

    Emrick, Michelle A; Sadilek, Martin; Konoki, Keiichi; Catterall, William A

    2010-10-26

    Ca(V)1 channels initiate excitation-contraction coupling in skeletal and cardiac muscle. During the fight-or-flight response, epinephrine released by the adrenal medulla and norepinephrine released from sympathetic nerves increase muscle contractility by activation of the β-adrenergic receptor/cAMP-dependent protein kinase pathway and up-regulation of Ca(V)1 channels in skeletal and cardiac muscle. Although the physiological mechanism of this pathway is well defined, the molecular mechanism and the sites of protein phosphorylation required for Ca(V)1 channel regulation are unknown. To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. Treatment of rabbits with isoproterenol to activate β-adrenergic receptors increased phosphorylation of S1575 in skeletal muscle Ca(V)1.1 channels in vivo, and treatment with propranolol to inhibit β-adrenergic receptors reduced phosphorylation. As S1575 and T1579 in Ca(V)1.1 channels and their homologs in Ca(V)1.2 channels are located at a key regulatory interface between the distal and proximal C-terminal domains, it is likely that phosphorylation of these sites in skeletal and cardiac muscle is directly involved in calcium channel regulation in response to the sympathetic nervous system in the fight-or-flight response.

  18. [Adrenergic beta-agonist intoxication].

    PubMed

    Carrola, Paulo; Devesa, Nuno; Silva, José Manuel; Ramos, Fernando; Alexandrino, Mário B; Moura, José J

    2003-01-01

    The authors describe two clinical cases (father and daughter), observed in the Hospital Urgency with distal tremors, anxiety, palpitations, nausea, headaches and dizziness, two hours after ingestión of cow liver. They also had leucocytosis (with neutrophylia), hypokalemia and hyperglycaemia. After treatment with potassium i.v. and propranolol, the symptoms disappeared. The symptoms recurred at home because the patients didn't take the prescribed medication and persisted for five days, with spontaneous disappearance. The serum of both patients revealed the presence of clenbuterol (65 hg/ml - father and 58 hg/ml - daughter). The animal's liver had a concentration of 1,42 mg/kg. Clenbuterol is a ß-adrenergic agonist with low specificity, with some veterinary indications. However, this substance has been illegally used as a growth's promotor. We intend to alert doctors for this problem, particularly those that work in the Urgency.

  19. Cadaveric nerve allotransplantation in the treatment of persistent thoracic neuralgia.

    PubMed

    Barbour, John R; Yee, Andrew; Moore, Amy M; Trulock, Elbert P; Buchowski, Jacob M; Mackinnon, Susan E

    2015-04-01

    When relief from neuralgia cannot be achieved with traditional methods, neurectomy may be considered to abate the stimulus, and primary opposition of the terminal nerve ending is recommended to prevent neuroma. Nerve repair with autograft is limited by autologous nerves available for large nerve defects. Cadaveric allografts provide an unlimited graft source without donor-site morbidities, but are rapidly rejected unless appropriate immunosuppression is achieved. An optimal treatment method for nerve allograft transplantation would minimize rejection while simultaneously permitting nerve regeneration. This report details a novel experience of nerve allograft transplantation using cadaveric nerve grafts to desensitize persistent postoperative thoracic neuralgia.

  20. Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes

    PubMed Central

    Yoon, Jin-Young; Jung, Seung-Ryoung; Hille, Bertil

    2014-01-01

    Melatonin secretion from the pineal gland is triggered by norepinephrine released from sympathetic terminals at night. In contrast, cholinergic and parasympathetic inputs, by activating nicotinic cholinergic receptors (nAChR), have been suggested to counterbalance the noradrenergic input. Here we investigated whether adrenergic signaling regulates nAChR channels in rat pinealocytes. Acetylcholine or the selective nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) activated large nAChR currents in whole cell patch-clamp experiments. Norepinephrine (NE) reduced the nAChR currents, an effect partially mimicked by a β-adrenergic receptor agonist, isoproterenol, and blocked by a β-adrenergic receptor antagonist, propranolol. Increasing intracellular cAMP levels using membrane-permeable 8-bromoadenosine (8-Br)-cAMP or 5,6-dichlorobenzimidazole riboside-3′,5′-cyclic monophosphorothioate (cBIMPS) also reduced nAChR activity, mimicking the effects of NE and isoproterenol. Further, removal of ATP from the intracellular pipette solution blocked the reduction of nAChR currents, suggesting involvement of protein kinases. Indeed protein kinase A inhibitors, H-89 and Rp-cAMPS, blocked the modulation of nAChR by adrenergic stimulation. After the downmodulation by NE, nAChR channels mediated a smaller Ca2+ influx and less membrane depolarization from the resting potential. Together these results suggest that NE released from sympathetic terminals at night attenuates nicotinic cholinergic signaling. PMID:24553185

  1. Upregulation of α1-adrenoceptors on cutaneous nerve fibres after partial sciatic nerve ligation and in complex regional pain syndrome type II.

    PubMed

    Drummond, Peter D; Drummond, Eleanor S; Dawson, Linda F; Mitchell, Vanessa; Finch, Philip M; Vaughan, Christopher W; Phillips, Jacqueline K

    2014-03-01

    After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of α1-adrenoceptors (α1-ARs) on these nerve fibres. To investigate this in the present study, changes in α1-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohistochemistry in an animal model of neuropathic pain involving partial ligation of the sciatic nerve. In addition, α1-AR expression on nerve fibres was examined in painful and unaffected skin of patients who developed complex regional pain syndrome (CRPS) after a peripheral nerve injury (CRPS type II). Four days after partial ligation of the sciatic nerve, α1-AR expression was greater on dermal nerve fibres that survived the injury than on dermal nerve fibres after sham surgery. This heightened α1-AR expression was observed on nonpeptidergic nociceptive afferents in the injured sciatic nerve, dermal nerve bundles, and the papillary dermis. Heightened expression of α1-AR in dermal nerve bundles after peripheral nerve injury also colocalized with neurofilament 200, a marker of myelinated nerve fibres. In each patient examined, α1-AR expression was greater on nerve fibres in skin affected by CRPS than in unaffected skin from the same patient or from pain-free controls. Together, these findings provide compelling evidence for an upregulation of α1-ARs on cutaneous nociceptive afferents after peripheral nerve injury. Activation of these receptors by circulating or locally secreted catecholamines might contribute to chronic pain in CRPS type II.

  2. Nerves and nerve endings in the skin of tropical cattle.

    PubMed

    Amakiri, S F; Ozoya, S E; Ogunnaike, P O

    1978-01-01

    The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable. PMID:76410

  3. Inferior alveolar and lingual nerve imaging.

    PubMed

    Miloro, Michael; Kolokythas, Antonia

    2011-03-01

    At present, there are no objective testing modalities available for evaluation of iatrogenic injury to the terminal branches of the trigeminal nerve, making such clinical diagnosis and management complicated for the oral and maxillofacial surgeon. Several imaging modalities can assist in the preoperative risk assessment of the trigeminal nerve as related to commonly performed procedures in the vicinity of the nerve, mostly third molar surgery. This article provides a review of all available imaging modalities and their clinical application relative to preoperative injury risk assessment of the inferior alveolar nerve and lingual nerve, and postinjury and postsurgical repair recovery status.

  4. The role of adenosine A2A and A3 receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve terminals.

    PubMed

    Donoso, M Verónica; Aedo, Felipe; Huidobro-Toro, J Pablo

    2006-03-01

    The pre-synaptic sympathetic modulator role of adenosine was assessed by studying transmitter release following electrical depolarization of nerve endings from the rat mesenteric artery. Mesentery perfusion with exogenous adenosine exclusively inhibited the release of norepinephrine (NA) but did not affect the overflow of neuropeptide Y (NPY), establishing the basis for a differential pre-synaptic modulator mechanism. Several adenosine structural analogs mimicked adenosine's effect on NA release and their relative order of potency was: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride = 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-d-ribofuranuronamide = 5'-(N-ethylcarboxamido)adenosine > adenosine > N(6)-cyclopentyladenosine. The use of selective receptor subtype antagonists confirmed the involvement of A(2A) and A(3) adenosine receptors. The modulator role of adenosine is probably due to the activation of both receptors; co-application of 1 nM 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride plus 1 nM 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-D-ribofuranuronamide caused additive reductions in NA released. Furthermore, while 1 nM of an A(2A) or A(3) receptor antagonist only partially reduced the inhibitory action of adenosine, the combined co-application of the two antagonists fully blocked the adenosine-induced inhibition. Only the simultaneous blockade of the adenosine A(2A) plus A(3) receptors with selective antagonists elicited a significant increase in NA overflow. H 89 reduced the release of both NA and NPY. We conclude that pre-synaptic A(2A) and A(3) adenosine receptor activation modulates sympathetic co-transmission by exclusively inhibiting the release of NA without affecting immunoreactive (ir)-NPY and we suggest separate mechanisms for vesicular release modulation.

  5. Modification by Beta-Adrenergic Blockade of the Circulatory Responses to Acute Hypoxia in Man*

    PubMed Central

    Richardson, David W.; Kontos, Hermes A.; Raper, A. Jarrell; Patterson, John L.

    1967-01-01

    In 17 healthy men, beta-adrenergic blockade reduced significantly the tachycardia and the elevation of cardiac output associated with inhalation of 7.5% oxygen for 7 to 10 minutes. Hypoxia did not increase plasma concentrations of epinephrine or norepinephrine in six subjects. Furthermore, blockade of alpha and beta receptors in the forearm did not modify the vasodilation in the forearm induced by hypoxia, providing pharmacologic evidence that hypoxia of the degree and duration used was not associated with an increase in the concentrations of circulating catecholamines in man. Part of the increase in cardiac output and heart rate during acute hypoxia in man is produced by stimulation of beta-adrenergic receptors, probably by cardiac sympathetic nerves. The mechanism of the vasodilation in the forearm during hypoxia remains uncertain. PMID:4381183

  6. Effects of (MET-5) enkephalin on the electrically-evoked mechanical responses in longitudinal and circular strips of the cat terminal ileum.

    PubMed

    Radomirov, R; Pencheva, N; Venkova, K; Davidoff, M

    1990-09-01

    In longitudinal and circular strips from cat terminal ileum field electrical stimulation at a frequency of 2 Hz evoked contractile responses. Stimulation at frequencies of 10 or 30 Hz elicited contractions of the longitudinal muscle and relaxations of the circular strips. (Met-5) enkephalin (1 nM) naloxone-dependently reduced the contractile and increased the inhibitory responses. Atropine (3 microM) converted the contractile responses to slight relaxations and potentiated the inhibitory responses. After atropine (3 microM) and guanethidine (50 microM) both longitudinal and circular strips responded to electrical stimulation with relaxations. In atropine-pretreated strips (Met-5) enkephalin was effective only in the circular strips, increasing the inhibitory responses. In contrast, after atropine and guanethidine (Met-5) enkephalin decreased these inhibitory responses. In unstimulated strips (Met-5) enkephalin failed to change the responses to acetylcholine and noradrenaline. It is concluded that (Met-5) enkephalin reduces the excitatory cholinergic components of the electrically-evoked responses in both longitudinal and circular strips as well as the excitatory adrenergic and the inhibitory non-adrenergic, non-cholinergic components of the responses in the circular strips by acting presynaptically. Demonstration of (Met-5) enkephalin-like immunoreactivity showed immunostaining in nerves of the myenteric plexus and in nerve fibers between the smooth muscle cells suggesting that (Met-5) enkephalin effects could be also of physiological significance.

  7. PLURIVESICULAR SECRETORY PROCESSES AND NERVE ENDINGS IN THE PINEAL GLAND OF THE RAT

    PubMed Central

    De Robertis, Eduardo; de Iraldi, Amanda Pellegrino

    1961-01-01

    The pineal body of white normal rats, 1.5 to 3 months old, was studied under the electron microscope. A single type of parenchymal cell—the pinealocyte—is recognized as the main component of the tissue, and some of the structural characteristics of the nucleus and cytoplasm are described. The main morphological characteristic of the pinealocytes is represented by club-shaped perivascular expansions connected to the cell by thin pedicles. They are found lying in a large, clear space surrounding the blood capillaries. The name plurivesicular secretory processes is proposed, to emphasize the main structural feature and the probable function of these cellular expansions. A tubulofibrillar component is mainly found in the pedicle, and within the expansion there are numerous small mitochondria and densily packed vesicles of about 425 A. Two types of vesicles, one with a homogeneous content and another with a very dense osmium deposit, are described. Between the two types there are intermediary forms. In these processes, mitochondria show profound changes which may lead to complete vacuolization. The significance of this plurivesicular secretory component is discussed in the light of recent work on the biogenic amines of the pineal body and preliminary experiments showing the release of the vesicles containing dense granules after treatment with reserpine. These vesicles are interpreted as the site of storage of some of the biogenic amines. Bundles of unmyelinated nerve fibers and endings on large blood vessels which also contain a plurivesicular content are described and tentatively interpreted as adrenergic nerve terminals. PMID:13720811

  8. Vagal non-adrenergic inhibition of guinea-pig stomach

    PubMed Central

    Beani, L.; Bianchi, Clementina; Crema, A.

    1971-01-01

    1. The effect of vagal and sympathetic stimulation on the mechanical and electrical activity (intracellular recording) of the body of the guinea-pig stomach was investigated in vitro. 2. Following atropine, 1 × 10-6-1 × 10-7 g/ml., vagal responses were reversed from excitatory to inhibitory. 3. Sympathetic blockade, produced by α- and β-receptor antagonists and adrenergic neurone-blocking agents, reduced or abolished sympathetic, but not vagal inhibition. 4. Hexamethonium (5 × 10-5 g/ml.) reduced vagal relaxation to 11-30% according to the stimulation rate. The residual response was maintained in the presence of 5-hydroxytryptamine tachyphylaxis. 5. Many muscle cells were observed to be under the influence of both vagus and sympathetic nerves: the effect of sympathetic stimulation was always inhibitory in nature, but high stimulation rates were required. The effect of vagal stimulation was both excitatory and inhibitory even in the absence of atropine: low stimulation rates gave rise either to E.J.P.s (excitatory junctional potentials), often followed by spikes, or to I.J.P.s (inhibitory junctional potentials). 6. In some spontaneously firing cells the interruption of electrical activity produced by vagal stimulation at 2/sec and sympathetic stimulation at 20/sec was recorded for a long enough time to check the effect of guanethedine (5 × 10-6 g/ml.): the drug selectively blocked sympathetic inhibition. 7. The significance of the inhibitory non-adrenergic transmitter, released by the intramural neurones activated by preganglionic vagal fibres, is discussed. PMID:4398576

  9. Structure, function, and regulation of adrenergic receptors.

    PubMed Central

    Strosberg, A. D.

    1993-01-01

    Adrenergic receptors for adrenaline and noradrenaline belong to the large multigenic family of receptors coupled to GTP-binding proteins. Three pharmacologic types have been identified: alpha 1-, alpha 2-, and beta-adrenergic receptors. Each of these has three subtypes, characterized by both structural and functional differences. The alpha 2 and beta receptors are coupled negatively and positively, respectively, to adenylyl cyclase via Gi or Gs regulatory proteins, and the alpha 1 receptors modulate phospholipase C via the Go protein. Subtype expression is regulated at the level of the gene, the mRNA, and the protein through various transcriptional and postsynthetic mechanisms. Adrenergic receptors constitute, after rhodopsin, one of the best studied models for the other receptors coupled to G proteins that are likely to display similar structural and functional properties. PMID:8401205

  10. Nerve conduction

    MedlinePlus

    ... fascicles) that contain hundreds of individual nerve fibers (neurons). Neurons consist of dendrites, axon, and cell body. The ... tree-like structures that receive signals from other neurons and from special sensory cells that sense the ...

  11. Adrenergic lipolysis in guinea pig is not a beta 3-adrenergic response: comparison with human adipocytes.

    PubMed

    Carpéné, C; Castan, I; Collon, P; Galitzky, J; Moratinos, J; Lafontan, M

    1994-03-01

    beta 3-Adrenoceptor agonists are potent lipolytic activators in rats, but they are only weak stimulators in human adipocytes, indicating interspecies differences in the adrenergic regulation of lipid mobilization. Like human but not rat adipocytes, guinea pig fat cells were poorly responsive to the beta 3-agonists BRL-37344, CGP-12177, SR-58611, and ICI-215001, acid metabolite of ICI-D7114. In guinea pigs, the beta 1-agonist dobutamine was more lipolytic than the beta 2-agonist procaterol. Anatomic location of fat deposits was without major influence on the beta-adrenergic responsiveness. Weak responses to beta 3-agonists were found whatever the sex or the age (from 2 days to 16 mo) of the animals. Even in the interscapular brown adipose tissue, which is well known in rats for its beta 3-adrenergic responsiveness, a blunted response to BRL-37344 was observed. The alpha 2-adrenergic antilipolytic effect and receptor number were smaller in guinea pig than in human adipocytes, but the beta-adrenergic receptor number was similar in the two species. Thus guinea pig adipocytes resemble human fat cells when their weak beta 3-adrenergic responsiveness is considered. PMID:7909205

  12. Dense-cored vesicles, smooth endoplasmic reticulum, and mitochondria are closely associated with non-specialized parts of plasma membrane of nerve terminals: implications for exocytosis and calcium buffering by intraterminal organelles.

    PubMed

    Lysakowski, A; Figueras, H; Price, S D; Peng, Y Y

    1999-01-18

    To determine whether there are anatomical correlates for intraterminal Ca2+ stores to regulate exocytosis of dense-cored vesicles (DCVs) and whether these stores can modulate exocytosis of synaptic vesicles, we studied the spatial distributions of DCVs, smooth endoplasmic reticulum (SER), and mitochondria in 19 serially reconstructed nerve terminals in bullfrog sympathetic ganglia. On average, each bouton had three active zones, 214 DCVs, 26 SER fragments (SERFs), and eight mitochondria. DCVs, SERFs and mitochondria were located, on average, 690, 624, and 526 nm, respectively, away from active zones. Virtually no DCVs were within "docking" (i.e., < or = 50 nm) distances of the active zones. Thus, it is unlikely that DCV exocytosis occurs at active zones via mechanisms similar to those for exocytosis of synaptic vesicles. Because there were virtually no SERFs or mitochondria within 50 nm of any active zone, Ca2+ modulation by these organelles is unlikely to affect ACh release evoked by a single action potential. In contrast, 30% of DCVs and 40% of SERFs were located within 50 nm of the nonspecialized regions of the plasma membrane. Because each bouton had at least one SERF within 50 nm of the plasma membrane and most of these SERFs had DCVs, but not mitochondria, near them, it is possible for Ca2+ release from the SER to provide the Ca2+ necessary for DCV exocytosis. The fact that 60% of the mitochondria had some part within 50 nm of the plasma membrane means that it is possible for mitochondrial Ca2+ buffering to affect DCV exocytosis.

  13. alpha- and beta-adrenergic receptor mechanisms in spontaneous contractile activity of rat ileal longitudinal smooth muscle.

    PubMed

    Seiler, Roland; Rickenbacher, Andreas; Shaw, Sidney; Balsiger, Bruno M

    2005-02-01

    Gastrointestinal motility is influenced by adrenergic modulation. Our aim was to identify specific subtypes of adrenergic receptors involved in inhibitory mechanisms that modulate gut smooth muscle contractile activity. Muscle strips of rat ileal longitudinal muscle were evaluated for spontaneous contractile activity and for equimolar dose-responses (10(-7) to 3 x 10(-5) M) to the adrenergic agents norepinephrine (nonselective agonist), phenylephrine (alpha(1)-agonist), clonidine (alpha(2)-agonist), prenalterol (beta(1)-agonist), ritodrine (beta(2)-agonist), and ZD7114 (beta(3)-agonist) in the presence and absence of tetrodotoxin (nonselective nerve blocker). Norepinephrine (3 x 10(-5) M) inhibited 65 +/- 6% (mean +/- SEM) of spontaneous contractile activity. The same molar dose of ritodrine, phenylephrine, or ZD7114 resulted in less inhibition (46 +/- 7%, 31 +/- 5%, and 39 +/- 3%, respectively; P < 0.05). The calculated molar concentration of ZD7114 needed to induce 50% inhibition was similar to that of norepinephrine, whereas higher concentrations of phenylephrine or ritodrine were required. Clonidine and prenalterol had no effect on contractile activity. Blockade of intramural neural transmission by tetrodotoxin affected the responses to ritodrine and phenylephrine (but not to norepinephrine or ZD7114), suggesting that these agents exert part of their effects via neurally mediated enteric pathways. Our results suggest that adrenergic modulation of contractile activity in the rat ileum is mediated primarily by muscular beta(3)-, beta(2)-, and alpha(1)-receptor mechanisms; the latter two also involve neural pathways. PMID:15694819

  14. Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement.

    PubMed

    Sato, T; Miyazawa, K; Suzuki, Y; Mizutani, Y; Uchibori, S; Asaoka, R; Arai, M; Togari, A; Goto, S

    2014-08-01

    Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.

  15. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  16. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  17. Microsurgical anatomy of the trochlear nerve.

    PubMed

    Joo, Wonil; Rhoton, Albert L

    2015-10-01

    The trochlear nerve is the cranial nerve with the longest intracranial course, but also the thinnest. It is the only nerve that arises from the dorsal surface of the brainstem and decussates in the superior medullary velum. After leaving the dorsal surface of the brainstem, it courses anterolaterally around the lateral surface of the brainstem and then passes anteriorly just beneath the free edge of the tentorium. It passes forward to enter the cavernous sinus, traverses the superior orbital fissure and terminates in the superior oblique muscle in the orbit. Because of its small diameter and its long course, the trochlear nerve can easily be injured during surgical procedures. Therefore, precise knowledge of its surgical anatomy and its neurovascular relationships is essential for approaching and removing complex lesions of the orbit and the middle and posterior fossae safely. This review describes the microsurgical anatomy of the trochlear nerve and is illustrated with pictures involving the nerve and its surrounding connective and neurovascular structures.

  18. Hypersomnolence with beta-adrenergic blockers.

    PubMed

    Thachil, J; Zeller, J R; Kochar, M S

    1987-11-01

    An elderly, mildly demented, hypertensive male patient developed hypersomnolence on administration of propranolol for treatment of hypertension; no other cause for hypersomnolence was detected. Upon replacement of propranolol with atenolol, he felt better but continued to be quite somnolent. When atenolol was discontinued, he reported to have lack of sleep. On readministration of subtherapeutic doses of the same beta-adrenergic blocking agents, he once again experienced excessive sleepiness. By discontinuing beta-blocking agents and introducing captopril, he felt much better, became pleasant and talkative, and blood pressure was well controlled. Beta antagonists are important drugs in the management of many cardiovascular problems. Propranolol, a lipophilic beta-blocking agent, and atenolol, a hydrophilic beta-blocking agent, are two of the major agents currently used clinically in the United States. Numerous neuropsychiatric side-effects of the beta-adrenergic blocking drugs have been reported, but hypersomnolence is not readily recognized as one of them. PMID:3665616

  19. Probing of β-adrenergic receptors by novel fluorescent β-adrenergic blockers

    PubMed Central

    Atlas, Daphne; Levitzki, Alexander

    1977-01-01

    The synthesis of two high-affinity fluorescent β-adrenergic blockers is described: dl-N1-[2-hydroxy-3-(1-naphthyloxy)propyl]-N2-(9-acridyl)-1,2-propanediamine (9-aminoacridylpropanolol, 9-AAP) and dl-N-[2-hydroxy-3-(1-naphthyloxy)propyl]-N′-dansylethylenediamine (dansyl analogue of propranolol, DAPN). Both 9-AAP and DAPN inhibit competitively the l-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in turkey erythrocyte membranes without affecting the fluoride-stimulated adenylate cyclase activity. Similarly, 9-AAP and DAPN inhibit in a competitive manner the binding of [125I]-iodohydroxybenzylpindolol to these β-adrenergic receptors. The two fluorescent β-adrenergic blockers 9-AAP and DAPN probe specifically β-adrenergic receptors in the central nervous system as well as in other organs when injected into rats. The fluorescence pattern can be monitored by fluorescence microscopy performed on cryostat slices of these organs. The appearance of the characteristic fluorescence pattern can be blocked in a stereospecific fashion by a prior injection of l-propranolol and not by a prior injection of d-propranolol. These compounds therefore offer a powerful means to map β-adrenergic receptors in vivo. The stereospecific displacement of 9-AAP from the β-adrenergic receptors of turkey erythrocyte membranes by l-propranolol and by l-epinephrine can be detected in vitro using front-face fluorescence. The potential use of these compounds to probe β-receptors in vitro and in vivo is discussed. Images PMID:23531

  20. Homologous beta-adrenergic desensitization in isolated rat hepatocytes.

    PubMed Central

    García-Sáinz, J A; Michel, B

    1987-01-01

    Hepatocytes from hypothyroid rats have a marked beta-adrenergic responsiveness. Preincubation of these hepatocytes with isoprenaline induced a time-dependent and concentration-dependent desensitization of the beta-adrenergic responsiveness without altering that to glucagon (homologous desensitization). The desensitization was evidenced both in the cyclic AMP accumulation and in the stimulation of ureagenesis induced by the beta-adrenergic agonists. Under the same conditions, preincubation with glucagon induced no desensitization. Propranolol was also unable to induce desensitization, but blocked that induced by isoprenaline. Pertussis-toxin treatment did not alter the homologous beta-adrenergic desensitization induced by isoprenaline. PMID:2825633

  1. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries

    PubMed Central

    Nausch, Lydia W. M.; Bonev, Adrian D.; Heppner, Thomas J.; Tallini, Yvonne; Kotlikoff, Michael I.

    2012-01-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction. PMID:22140050

  2. Chronic sympathetic innervation of islets in transgenic mice results in differential desensitization of alpha-adrenergic inhibition of insulin secretion.

    PubMed

    Grodsky, G M; Ma, Y H; Edwards, R H

    1997-01-01

    The effects of chronic sympathetic hyperinnervation on pancreatic beta-cell insulin secretion were investigated utilizing the in vitro perfused pancreas from transgenic mice. These mice exhibit islet hyperinnervation of sympathetic neurons resulting from overexpression of nerve growth factor in their beta-cells (1). The goal was to determine whether sympathetic hyperinnervation increased classic alpha-adrenergic inhibition of beta-cell insulin secretion or, in contrast, down-regulated beta-cell sensitivity to adrenergic input resulting in enhanced insulin secretion. Both fasting and fed blood sugars and pancreatic insulin content were normal in the transgenics. Response of the transgenic perfused pancreas to low glucose (7 mM) was primarily first phase and normal whereas high glucose (22 mM) caused enhanced, rather than reduced, insulin secretion of both first and second phases. The alpha-antagonist, phentolamine, caused a six-fold increase in glucose-stimulated insulin secretion from the control pancreas, an effect that was blunted for the transgenic pancreas. A similarly blunted response to phentolamine occurred when this agent was superimposed on a combined glucose-forskolin stimulus. (The positive effect on insulin secretion by phentolamine in normal beta-cell preparations has arguably been ascribed to non-specific ionic effects.) Therefore, as a test of possible changes in the ATP regulated K+ channel or the linked Ca++ channels, glyburide was perfused during glucose stimulation. Insulin secretion in response to glyburide was increased two fold in the control pancreas. However, with the transgenic pancreas, in contrast to the enhanced response to glucose, the effect of glyburide was almost completely inhibited. It is concluded that: 1) chronic adrenergic hyperinnervation results in enhanced glucose-stimulated insulin secretion by desensitization of a major alpha-adrenergic inhibitory site(s); and 2) adrenergic hyperinnervation acts directly or indirectly on

  3. [Anatomical study of the cavernous nerve in relation to nerve sparing operation].

    PubMed

    Hanawa, K

    1994-08-01

    Recently, nerve sparing radical prostatectomy has became widely considered as the primary goal for maintaining a high standard of quality of life (QOL). However, anatomical localization of the cavernous nerve has not yet been precisely clarified in terms of the terminal end in the corpus cavernous penis distal to the urogenital membrane. Here in attempt to demonstrate the precise localization of the cavernous nerve, in six adult male cadaver. The cavernous nerves ran between the prostatic capsule and the prostatic fascia, through the capsule of the seminal vesicle. The nerves penetrated the membranous urethra at 8 mm from the margin of the urethra at the position of 5 and 7 o'clock. Therefore, the following procedures are critical to achieve successful nerve sparing: 1) meticulous division of the seminal-vesicle, 2) precise separation of the neurovascular bundle between the prostatic capsule and fascia, and 3) the careful transaction of the membranous urethra.

  4. Has iprindole an alpha adrenergic activity?

    PubMed

    Ganry, H; Bourin, M

    1993-05-01

    1. Acute administration of iprindole potentiated the toxicity of 1-norepinephrine and increased the intensity of oxotremorine-induced tremors. 2. On the forced swimming test combination iprindole with imipramine reduced the duration of immobility. 3. The action of yohimbine on the locomotor activity was antagonized by a pre-injection of iprindole. 4. Iprindole increased and prolonged exophthalmia and loss of righting reflex induced by xylazine. 5 All these results seems indicate that iprindole has an indirect alpha 1 and alpha 2 adrenergic activity.

  5. Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

    PubMed

    Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

    2015-01-01

    Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

  6. Agonistic autoantibodies to the α(1) -adrenergic receptor and the β(2) -adrenergic receptor in Alzheimer's and vascular dementia.

    PubMed

    Karczewski, P; Hempel, P; Kunze, R; Bimmler, M

    2012-05-01

    Although primary causes of Alzheimer's and vascular dementia are unknown, the importance of preceding vascular lesions is widely accepted. Furthermore, there is strong evidence for the involvement of autoimmune mechanisms. Here, we report the presence of agonistic autoantibodies directed at adrenergic receptors in the circulation of patients with mild to moderate Alzheimer's and vascular dementia. In 59% of these patients, agonistic autoantibodies against the α(1) -adrenergic receptor and the β(2) -adrenergic receptor were identified. The majority of positive patients (66%) contained both types of autoantibodies in combination. In a control group of patients with neurological impairments others than Alzheimer's and vascular dementia, only 17% were found to harbour these autoantibodies. The autoantibodies to the α(1) -adrenergic receptor interacted preferably with the extracellular loop1 of the receptor. They were further studied in IgG preparations from the column regenerate of a patient who underwent immunoadsorption. The α(1) -adrenergic receptor autoantibodies specifically bound to the extracellular loop1 peptide of the receptor with an apparent EC(50) value of 30 nm. They mobilized intracellular calcium in a clonal cell line expressing the human form of the α(1) -adrenergic receptor. Our data support the notion that autoimmune mechanisms play a significant role in the pathogenesis of Alzheimer's and vascular dementia. We suggest that agonistic autoantibodies to the α(1) -adrenergic and the β(2) -adrenergic receptor may contribute to vascular lesions and increased plaque formation.

  7. Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New Tool for Nerve Surgeons?

    PubMed Central

    Liao, Joseph C; Curtin, Catherine M

    2015-01-01

    Peripheral nerve injuries remain a challenge for reconstructive surgeons with many patients obtaining suboptimal results. Understanding the level of injury is imperative for successful repair. Current methods for distinguishing healthy from damaged nerve are time consuming and possess limited efficacy. Confocal laser endomicroscopy (CLE) is an emerging optical biopsy technology that enables dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic nerve was either left undamaged or briefly clamped to simulate injury. Diluted fluorescein was applied topically to the nerve. CLE imaging was performed by direct contact of the probe with nerve tissue. Images representative of both damaged and undamaged nerve fibers were collected and compared to routine H&E histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve fibers, distinct from surrounding adipose and connective tissue. When damaged, these bands appear truncated and terminate in blebs of opacity. H&E staining revealed similar features in damaged nerve fibers. These results prompt development of a protocol for imaging peripheral nerves intraoperatively. To this end, improving surgeons' ability to understand the level of injury through real-time imaging will allow for faster and more informed operative decisions than the current standard permits. PMID:26430636

  8. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  9. Adrenergic regulation of innate immunity: a review

    PubMed Central

    Scanzano, Angela; Cosentino, Marco

    2015-01-01

    The sympathetic nervous system has a major role in the brain-immune cross-talk, but few information exist on the sympathoadrenergic regulation of innate immune system. The aim of this review is to summarize available knowledge regarding the sympathetic modulation of the innate immune response, providing a rational background for the possible repurposing of adrenergic drugs as immunomodulating agents. The cells of immune system express adrenoceptors (AR), which represent the target for noradrenaline and adrenaline. In human neutrophils, adrenaline and noradrenaline inhibit migration, CD11b/CD18 expression, and oxidative metabolism, possibly through β-AR, although the role of α1- and α2-AR requires further investigation. Natural Killer express β-AR, which are usually inhibitory. Monocytes express β-AR and their activation is usually antiinflammatory. On murine Dentritic cells (DC), β-AR mediate sympathetic influence on DC-T cells interactions. In human DC β2-AR may affect Th1/2 differentiation of CD4+ T cells. In microglia and in astrocytes, β2-AR dysregulation may contribute to neuroinflammation in autoimmune and neurodegenerative disease. In conclusion, extensive evidence supports a critical role for adrenergic mechanisms in the regulation of innate immunity, in peripheral tissues as well as in the CNS. Sympathoadrenergic pathways in the innate immune system may represent novel antiinflammatory and immunomodulating targets with significant therapeutic potential. PMID:26321956

  10. Differences in affinity of cardiac beta-adrenergic receptors for (3H)dihydroalprenolol

    SciTech Connect

    Muntz, K.H.; Calianos, T.A.; Vandermolen, D.T.; Willerson, J.T.; Buja, L.M.

    1986-03-01

    We performed quantitative light microscopic autoradiography of (3H)dihydroalprenolol (DHA) binding to frozen sections of canine myocardium to test the hypothesis that there are differences in the density or affinity of beta-adrenergic receptors on various tissue compartments. In one study, with concentrations of (3H)DHA from 0.34 to 5.1 nM, specific binding to cardiac myocytes was saturable, whereas nonspecific binding was linear with ligand concentration. Arterioles had more specific grain counts than muscle cells (P less than 0.0001), and Scatchard analysis showed that the arterioles had a much higher affinity for (3H)DHA than myocytes. In a second study with lower concentrations of (3H)DHA (0.19-1.98 nM), binding to the arterioles saturated, whereas binding to the cardiac myocytes did not. Specific binding to arterioles was significantly higher (P less than 0.0001) than binding to myocytes at all concentrations of (3H)DHA. The dissociation constants for the subendocardial and subepicardial myocytes were 1.57 and 1.71 nM, respectively, while the dissociation constant for the arterioles was 0.26 nM. The maximum number of binding sites was 911 grains/0.9 X 10(-2) mm2 for subepicardial myocytes, 936 for subendocardial myocytes, and 986 for arterioles. The large nerves accompanying an epicardial artery also demonstrated specific (3H)DHA binding. Thus this study has demonstrated major differences in the distribution and affinity of beta-adrenergic receptors, which may help to explain various physiological responses to beta-adrenergic stimulation.

  11. MELANOPHORE BANDS AND AREAS DUE TO NERVE CUTTING, IN RELATION TO THE PROTRACTED ACTIVITY OF NERVES

    PubMed Central

    Parker, G. H.

    1941-01-01

    1. When appropriate chromatic nerves are cut caudal bands, cephalic areas, and the pelvic fins of the catfish Ameiurus darken. In pale fishes all these areas will sooner or later blanch. By recutting their nerves all such blanched areas will darken again. 2. These observations show that the darkening of caudal bands, areas, and fins on cutting their nerves is not due to paralysis (Brücke), to the obstruction of central influences such as inhibition (Zoond and Eyre), nor to vasomotor disturbances (Hogben), but to activities emanating from the cut itself. 3. The chief agents concerned with the color changes in Ameiurus are three: intermedin from the pituitary gland, acetylcholine from the dispersing nerves (cholinergic fibers), and adrenalin from the concentrating nerves (adrenergic fibers). The first two darken the fish; the third blanches it. In darkening the dispersing nerves appear to initiate the process and to be followed and substantially supplemented by intermedin. 4. Caudal bands blanch by lateral invasion, cephalic areas by lateral invasion and internal disintegration, and pelvic fins by a uniform process of general loss of tint equivalent to internal disintegration. 5. Adrenalin may be carried in such an oil as olive oil and may therefore act as a lipohumor; it is soluble in water and hence may act as a hydrohumor. In lateral invasion (caudal bands, cephalic areas) it probably acts as a lipohumor and in internal disintegration (cephalic areas, pelvic fins) it probably plays the part of a hydrohumor. 6. The duration of the activity of dispersing nerves after they had been cut was tested by means of the oscillograph, by anesthetizing blocks, and by cold-blocks. The nerves of Ameiurus proved to be unsatisfactory for oscillograph tests. An anesthetizing block, magnesium sulfate, is only partly satisfactory. A cold-block, 0°C., is successful to a limited degree. 7. By means of a cold-block it can be shown that dispersing autonomic nerve fibers in Ameiurus can

  12. Cholinergic and adrenergic influence on the teleost heart in vivo.

    PubMed

    Axelsson, M; Ehrenström, F; Nilsson, S

    1987-01-01

    The tonical cholinergic and adrenergic influence on the heart rate was investigated in vivo in seven species of marine teleosts (pollack, Pollachius pollachius; cuckoo wrasse, Labrus mixtus; ballan wrasse, Labrus berggylta; five-bearded rockling, Ciliata mustela; tadpole fish, Raniceps raninus; eel-pout, Zoarces viviparus and short-spined sea scorpion, Myoxocephalus scor pius) during rest and, in two of the species (P. pollachius and L. mixtus), also during moderate swimming exercise in a Blazka-type swim tunnel. Ventral aortic blood pressure and heart rate were recorded via a catheter implanted in an afferent branchial artery, and the influence of the cholinergic and adrenergic tonus on the heart rate was assessed by injection of atropine and sotalol respectively. During rest the adrenergic tonus was higher than the cholinergic tonus in all species except L. berggylta, where the reverse was true. In P. pollachius and L. mixtus, exercise appeared to produce a lowering of the cholinergic tonus on the heart and, possibly, a slight increase of the adrenergic tonus. The nature of the adrenergic tonus (humoral or neural) is not clear, but the low plasma concentrations of catecholamines both during rest and exercise could be interpreted in favour of a mainly neural adrenergic tonus on the teleost heart. These experiments are compatible with the view that both a cholinergic inhibitory tonus and an adrenergic excitatory tonus are general features in the control of the teleost heart in vivo, both at rest and during moderate swimming exercise.

  13. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.

    PubMed

    Baker, Candice N; Gidus, Sarah A; Price, George F; Peoples, Jessica N R; Ebert, Steven N

    2015-03-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. PMID:25516547

  14. Cocaine downregulates beta-adrenergic receptors in pregnant sheep myometrium.

    PubMed

    Wang, F L; Gauvin, J M; Dombrowski, M P; Smith, Y R; Christopher, K A; Hurd, W W

    1996-01-01

    Cocaine abuse is associated with premature labor. Although cocaine is known to competitively inhibit beta-adrenergic receptor binding, cocaine's effect on receptor downregulation is uncertain. This study was designed to determine the in vitro effect of cocaine on downregulation of beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myometrium was incubated with either cocaine, isoproterenol, or a cocaine metabolite, benzoylecgonine. Membrane fractions were assayed for beta-adrenergic receptors using (125I)-cyanopindolol and the beta 2-adrenergic antagonist ICI 118,551. We found that cocaine (10(-6) to 10(-4) mol/L), but not benzoylecgonine, downregulated both beta 1- and beta 2-adrenergic receptors, but did not further augment receptor downregulation by isoproterenol. The 46% decrease in beta-adrenergic receptors seen after exposure to cocaine was similar to the 53% decrease seen after isoproterenol. We hypothesize downregulation of beta-adrenergic receptors by cocaine may play a role in the association of cocaine abuse with premature labor.

  15. Cholinergic inhibition of adrenergic neurosecretion in the rabbit iris-ciliary body

    SciTech Connect

    Jumblatt, J.E.; North, G.T.

    1988-04-01

    The prejunctional effects of cholinergic agents on release of norepinephrine from sympathetic nerve endings were investigated in the isolated, superfused rabbit iris-ciliary body. Stimulation-evoked release of /sup 3/H-norepinephrine was inhibited by the cholinergic agonists methacholine, oxotremorine, muscarine, carbamylcholine and acetylcholine (plus eserine), but was unmodified by pilocarpine or nicotine. Agonist-induced inhibition was antagonized selectively by atropine, indicating a muscarinic response. Atropine alone markedly enhanced norepinephrine release, revealing considerable tonic activation of prejunctional cholinergic receptors in this system. Prejunctional inhibition by carbamylcholine was found to completely override the facilitative action of forskolin or 8-bromo-cyclic AMP on neurotransmitter release. Cholinergic and alpha 2-adrenergic effects on neurosecretion were non-additive, suggesting that the underlying receptors coexist at neurotransmitter release sites.

  16. Secondary optic nerve tumors.

    PubMed

    Christmas, N J; Mead, M D; Richardson, E P; Albert, D M

    1991-01-01

    Secondary tumors of the optic nerve are more common than primary optic nerve tumors. The involvement of the optic nerve may arise from direct invasion from intraocular malignancies, from hematopoietic malignancy, from meningeal carcinomatosis, or from distant primary tumors. Orbital tumors rarely invade the optic nerve, and brain tumors involve it only in their late stages.

  17. Adrenergic receptors in human fetal liver membranes.

    PubMed

    Falkay, G; Kovács, L

    1990-01-01

    The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using 3H-prazosin and 3H-dihydroalprenolol, respectively, as radioligand. Heterogenous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycaemia of newborns after treatment of premature labour with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.

  18. Involvement of the orexin system in sympathetic nerve regulation.

    PubMed

    Murakami, Manabu; Ohba, Takayoshi; Kushikata, Testuya; Niwa, Hidetoshi; Kurose, Akira; Imaizumi, Tadaatsu; Watanabe, Hiroyuki; Yanagisawa, Teruyuki; Nakaji, Shigeyuki; Ono, Kyoichi; Hirota, Kazuyoshi

    2015-05-15

    Orexin, also known as hypocretin, is a secreted neuropeptide implicated in the regulation of sleep and food intake. In the present study, we examined the importance of orexin in regulation of the sympathetic nervous system using an orexin/ataxin-3 transgenic (OXTg) rat, which has a minimal number of orexin neurons. RT-PCR analysis identified expression of prepro-orexin and orexin receptor-1 (OX1R) in the superior cervical ganglion (SCG), and expression of another receptor (OX2R) was marginal in the wild-type rat. The orexin/ataxin-3 transgenic rat showed increased expression of OX1R and OX2R, whereas expression of prepro-orexin was undetectable, suggesting a compensatory increase in both receptors. In the ECG recording (R-R interval), orexin/ataxin-3 transgenic rats showed decreased responsiveness to the β-adrenergic blocker propranolol. Furthermore, OXTg rats had deteriorated R-R interval regulation, indicating involvement of the orexin system in sympathetic nerve regulation. This was accompanied by decreased baroreflex and responsiveness to β-adrenergic blocker in blood pressure recording, also suggesting involvement of the orexin system in sympathetic nerve regulation. Histological examination revealed hypotrophic changes in the transgenic heart, suggesting involvement of the orexin system in cardiac development. Taken together, our present results indicate involvement of the orexin system in sympathetic nerve control.

  19. Termination Documentation

    ERIC Educational Resources Information Center

    Duncan, Mike; Hill, Jillian

    2014-01-01

    In this study, we examined 11 workplaces to determine how they handle termination documentation, an empirically unexplored area in technical communication and rhetoric. We found that the use of termination documentation is context dependent while following a basic pattern of infraction, investigation, intervention, and termination. Furthermore,…

  20. Beta-adrenergic receptor sensitivity in subjects practicing transcendental meditation.

    PubMed

    Mills, P J; Schneider, R H; Hill, D; Walton, K G; Wallace, R K

    1990-01-01

    Several studies suggest that behavioral techniques such as meditation and relaxation may be associated with reduced end organ adrenergic receptor sensitivity. Thus far the evidence supporting this hypothesis has been indirect. We present preliminary findings showing reduced beta-adrenergic receptor sensitivity in a group of subjects practicing Transcendental Meditation. The meditation group (N = 10), compared to controls (N = 10), had a lower percentage of functional lymphocyte beta-adrenergic receptors (p = 0.009), but showed no difference in total receptor number or plasma catecholamines. There were no differences between the groups in Type A behavior, the Type A components, exercise, or family history of hypertension. The results provide some support for studies postulating that meditation is associated with reduced sympathetic adrenergic receptor sensitivity, and provide encouragement for the efficacy of receptor measurement in psychophysiology research.

  1. Pharmacologic specificity of alpha-2 adrenergic receptor subtypes

    SciTech Connect

    Petrash, A.; Bylund, D.

    1986-03-01

    The authors have defined alpha-2 adrenergic receptor subtypes in human and rat tissues using prazosin as a subtype selective drug. Prazosin has a lower affinity (250 nM) at alpha-2A receptor and a higher affinity (5 nM) at alpha-2B receptors. In order to determine if other adrenergic drugs are selective for one or the other subtypes, the authors performed (/sup 3/H)yohimbine inhibition experiments with various adrenergic drugs in tissues containing alpha-2A, alpha-2B or both subtypes. Oxymetazoline, WB4101 and yohimbine were found to be 80-, 20- and 10-fold more potent at alpha-2A receptors than at alpha-2B receptors. Phentolamine, adazoxan, (+)- and (-)-mianserin, clonidine, (+)-butaclamol, (-)- and (+)-norepinephrine, epinephrine, dopamine and thioridazine were found to have equal affinities for the two subtypes. These results further validate the subdivision of alpha-2 adrenergic receptors into alpha-2A and alpha-2B subtypes.

  2. Rabbit alveolar beta-adrenergic receptors increase with gestational age.

    PubMed

    Lewis, V; Goldfien, A C; Day, J P; Roberts, J M

    1990-01-01

    Pulmonary beta-adrenergic receptors, which mediate the actions of endogenous catecholamines, increase before birth, an important step in pulmonary maturation. This increase, which occurs primarily in the alveoli, may be hastened by corticosteroids. However, because the lung is composed of more than 40 cell types, we asked whether the normal distribution of beta-adrenergic receptors changes with gestational age in a way that seems physiologically relevant. We compared lungs from fetal rabbits at 26 and 31 days' gestation with lungs from adult rabbits by autoradiography with 125iodocyanopindolol, a beta-adrenergic antagonist. While the total silver grain concentration increased during gestation, the greatest proportional increase occurred in the alveoli. We conclude that pulmonary beta-adrenergic receptor concentration increases during gestation and that this increase is most dramatic for alveoli. This pattern is consistent with that previously observed after treatment of fetal rabbits in utero with corticosteroids.

  3. Effects of intranasal cocaine on sympathetic nerve discharge in humans.

    PubMed Central

    Jacobsen, T N; Grayburn, P A; Snyder, R W; Hansen, J; Chavoshan, B; Landau, C; Lange, R A; Hillis, L D; Victor, R G

    1997-01-01

    Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these

  4. Nerve Injuries in Athletes.

    PubMed

    Collins, K; Storey, M; Peterson, K; Nutter, P

    1988-01-01

    In brief: Nerve injuries in athletes may be serious and may delay or prevent an athlete's return to his or her sport. Over a two-year period, the authors evaluated the condition of 65 patients who had entrapments of a nerve or nerve root, documented with electromyography. They describe four case histories: Two patients had radial nerve entrapments, one caused by baseball pitching and the other by kayaking; one football player had combined suprascapular neuropathy and upper trunk brachial plexopathy; and one patient had carpal tunnel syndrome of a median nerve secondary to rowing. Sports-related peripheral nerve lesions of the lower extremity were not seen during the study period. Based on a literature review, the nerve injuries discussed represent the spectrum of nerve entrapments likely to be seen in US clinics. The authors conclude that peripheral nerve lesions should be considered in the differential diagnosis of sports injuries, particularly at the shoulder, elbow, and wrist.

  5. Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

    PubMed Central

    Reyes, B.A.S.; Szot, P.; Sikkema, C.; Cathel, A. M.; Kirby, L.G.; Van Bockstaele, E.J.

    2014-01-01

    The cannabinoid receptor agonist, WIN 55,212-2, increases extracellular norepinephrine levels in the rat frontal cortex under basal conditions, likely via desensitization of inhibitory α2-adrenergic receptors located on norepinephrine terminals. Here, the effect of WIN 55,212-2 on stress-induced norepinephrine release was assessed in the medial prefrontal cortex (mPFC), in adult male Sprague-Dawley rats using in vivo microdialysis. Systemic administration of WIN 55,212-2 thirty minutes prior to stressor exposure prevented stress-induced cortical norepinephrine release induced by a single exposure to swim when compared to vehicle. To further probe cortical cannabinoid-adrenergic interactions, postsynaptic α2-adrenergic receptor (AR)-mediated responses were assessed in mPFC pyramidal neurons using electrophysiological analysis in an in vitro cortical slice preparation. We confirm prior studies showing that clonidine increases cortical pyramidal cell excitability and that this was unaffected by exposure to acute stress. WIN 55,212-2, via bath application, blocked postsynaptic α2-AR mediated responses in cortical neurons irrespective of exposure to stress. Interestingly, stress exposure prevented the desensitization of α2-AR mediated responses produced by a history of cannabinoid exposure. Together, these data indicate the stress-dependent nature of cannabinoid interactions via both pre- and postsynaptic ARs. In summary, microdialysis data indicate that cannabinoids restrain stress-induced cortical NE efflux. Electrophysiology data indicate that cannabinoids also restrain cortical cell excitability under basal conditions; however, stress interferes with these CB1-α2 AR interactions, potentially contributing to over-activation of pyramidal neurons in mPFC. Overall, cannabinoids are protective of the NE system and cortical excitability but stress can derail this protective effect, potentially contributing to stress-related psychopathology. These data add to the

  6. Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype

    SciTech Connect

    Wilson, A.L.; Seibert, K.; Brandon, S.; Cragoe, E.J. Jr.; Limbird, L.E. )

    1991-04-01

    The unglycosylated alpha 2B subtype of the alpha 2-adrenergic receptor found in NG-108-15 cells possesses allosteric regulation of adrenergic ligand binding by monovalent cations and 5-amino-substituted amiloride analogs. These findings demonstrate that allosteric modulation of adrenergic ligand binding is not a property unique to the alpha 2A subtype. The observation that amiloride analogs as well as monovalent cations can modulate adrenergic ligand binding to the nonglycosylated alpha 2B subtype indicates that charge shielding due to carbohydrate moieties does not play a role in this allosteric modulation but, rather, these regulatory effects result from interactions of cations and amiloride analogs with the protein moiety of the receptor. Furthermore, the observation that both alpha 2A and alpha 2B receptor subtypes are modulated by amiloride analogs suggests that structural domains that are conserved between the two are likely to be involved in this allosteric modulation.

  7. Teeth and tooth nerves.

    PubMed

    Hildebrand, C; Fried, K; Tuisku, F; Johansson, C S

    1995-02-01

    support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7777672

  8. β-adrenergic antagonists influence abdominal aorta contractility by mechanisms not involving β-adrenergic receptors.

    PubMed

    Hauzer, Willy; Bujok, Jolanta; Czerski, Albert; Rusiecka, Agnieszka; Pecka, Ewa; Gnus, Jan; Zawadzki, Wojciech; Witkiewicz, Wojciech

    2014-01-01

    β-adrenergic receptors (β-AR) are widely distributed in the cardiovascular system, where they considerably contribute to the control of its functions. β-blockers are commonly used in the treatment of disorders of the circulatory system. They act primarily by inhibiting cardiac β-receptors. However, there are also reports of pleiotropic action of β-blockers as well as of new compounds created to study β3 adrenergic receptors. The study aimed to investigate additional mechanisms of action of β-AR inhibitors in the rabbit abdominal aorta with emphasis on their action on α-adrenergic receptors and calcium influx. Responses to propranolol, betaxolol, metoprolol and SR59230A were evaluated in phenylephrine and PGF(2alpha) precontracted aortic rings. The effect of propranolol on the phenylephrine concentration-contraction curve was examined. Propranolol (≥ 10 μM) and SR59230A (≥ 0.1 μM) induced relaxations in phenylephrine-precontracted rings, while betaxolol and metoprolol had little effect. The β-AR inhibitors produced further contraction of tissues preincubated with PGF(2alpha), excluding SR59230A, which after initial contraction, elicited marked relaxation at a concentration above 1 ĕM. 100 μM of propranolol caused a significant rightward shift of the concentration-contraction curve to phenylephrine with no reduction in the maximum response. Incubation of aortic rings in phentolamine reduced the maximal contraction to propranolol; verapamil pretreatment by contrast enhanced contractile response. In conclusion, SR59230A and propranolol most probably act as α1-AR competitive antagonists in the presence of phenylephrine in rabbit abdominal aortic rings. After α-ARs blockade, propranolol exerts a weak relaxing activity connected with Ca2+ channel inactivation. SR59230A at a high concentration acts on the rabbit aorta by an additional mechanism needing further investigation.

  9. Nerve injuries about the elbow in the athlete.

    PubMed

    Harris, Joshua D; Lintner, David M

    2014-09-01

    The athlete's elbow is a remarkable example of motion, strength, and durability. The stress placed on the elbow during sport, including the throwing motion, may lead to soft-tissue ligamentous and nerve injury. The thrower's elbow illustrates one example of possible nerve injury about the elbow in sport, related to chronic repetitive tensile and compressive stresses to the ulnar nerve associated with elbow flexion and valgus position. Besides the throwing athlete, nerve injury from high-energy direct-impact forces may also damage nerves around the elbow in contact sports. Detailed history and physical examination can often make the diagnosis of most upper extremity neuropathies. The clinician must be aware of the possibility of isolated or combined nerve injury as far proximal as the cervical nerve roots, through the brachial plexus, to the peripheral nerve terminal branches. Electrodiagnostic studies are occasionally beneficial for diagnosis with certain nerves. Nonoperative management is often successful in most elbow and upper extremity neuropathies. If conservative treatment fails, then surgical treatment should address all potentially offending structures. In the presence of medial laxity and concurrent ulnar neuritis, the medial ulnar collateral ligament warrants surgical treatment, in addition to transposition of the ulnar nerve. The morbidity of open surgical decompression of nerves in and around the elbow is potentially career threatening in the throwing athlete. This mandates an assessment of the adequacy of the nonsurgical treatment and a thorough preoperative discussion of the risks and benefits of surgery.

  10. Nerve injuries about the elbow in the athlete.

    PubMed

    Harris, Joshua D; Lintner, David M

    2014-09-01

    The athlete's elbow is a remarkable example of motion, strength, and durability. The stress placed on the elbow during sport, including the throwing motion, may lead to soft-tissue ligamentous and nerve injury. The thrower's elbow illustrates one example of possible nerve injury about the elbow in sport, related to chronic repetitive tensile and compressive stresses to the ulnar nerve associated with elbow flexion and valgus position. Besides the throwing athlete, nerve injury from high-energy direct-impact forces may also damage nerves around the elbow in contact sports. Detailed history and physical examination can often make the diagnosis of most upper extremity neuropathies. The clinician must be aware of the possibility of isolated or combined nerve injury as far proximal as the cervical nerve roots, through the brachial plexus, to the peripheral nerve terminal branches. Electrodiagnostic studies are occasionally beneficial for diagnosis with certain nerves. Nonoperative management is often successful in most elbow and upper extremity neuropathies. If conservative treatment fails, then surgical treatment should address all potentially offending structures. In the presence of medial laxity and concurrent ulnar neuritis, the medial ulnar collateral ligament warrants surgical treatment, in addition to transposition of the ulnar nerve. The morbidity of open surgical decompression of nerves in and around the elbow is potentially career threatening in the throwing athlete. This mandates an assessment of the adequacy of the nonsurgical treatment and a thorough preoperative discussion of the risks and benefits of surgery. PMID:25077754

  11. Tissue specific effects of the beta 2-adrenergic agonist salbutamol on LPS-induced IFN-gamma, IL-10 and TGF-beta responses in vivo.

    PubMed

    Eijkelkamp, Niels; Cobelens, Pieter M; Sanders, Virginia M; Heijnen, Cobi J; Kavelaars, Annemieke

    2004-05-01

    Beta2-adrenergic agonists have immunomodulatory effects both in vitro and in vivo. We describe that oral salbutamol (beta-adrenergic agonist) administration has tissue-specific effects on cytokine production induced by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration. Salbutamol reduced LPS-induced IFN-gamma levels at both mucosal and non-mucosal sites. However, salbutamol increased IL-10 levels in the peritoneal cavity, but decreased levels in terminal ileum and lung. Salbutamol did not alter LPS-induced TGF-beta levels in the terminal ileum, but increased levels in liver and peritoneal cavity. Thus, orally administered salbutamol decreases LPS-induced IFN-gamma levels in all tissues tested, but has tissue specific effects on IL-10 and TGF-beta levels.

  12. Communications Between the Trigeminal Nerve and the Facial Nerve in the Face: A Systematic Review.

    PubMed

    Hwang, Kun; Yang, Su Cheol; Song, Ju Sung

    2015-07-01

    The aim of the article is to elucidate the communications between the trigeminal nerve and facial nerve in the face. In a PubMed search, 328 studies were found using the terms 'trigeminal nerve, facial nerve, and communication.' The abstracts were read and 39 full-text articles were reviewed. Among them, 11 articles were analyzed. In the studies using dissection, the maxillary branch (V2) had the highest frequency (95.0% ± 8.0%) of communication with the facial nerve, followed by the mandibular branch (V3) (76.7% ± 38.5%). The ophthalmic branch (V1) had the lowest frequency of communication (33.8% ± 19.5%). In a Sihler stain, all of the maxillary branches and mandibular branches had communications with the facial nerve and 85.7% (12/14 hemifaces) of the ophthalmic branches had communications. The frequency of communications between the trigeminal nerve and facial nerve were significantly higher (P = 0.00, t-test) in the studies using a Sihler stain (94.7% ± 1.1%) than the studies using dissection (76.9 ± 35.8). The reason for the significantly higher frequency of trigeminal-facial communication in the studies using a Sihler stain is because of the limitation of the Sihler stain itself. This technique cannot differentiate the motor nerves from sensory nerves at the periphery, and a crossover can be misinterpreted as communication near to nerve terminal.

  13. Common peroneal nerve dysfunction

    MedlinePlus

    ... toe-out movements Tests of nerve activity include: Electromyography (EMG, a test of electrical activity in muscles) Nerve ... Peroneal neuropathy. In: Preston DC, Shapiro BE, eds. Electromyography and Neuromuscular Disorders . 3rd ed. Philadelphia, PA: Elsevier; ...

  14. Nerve conduction velocity

    MedlinePlus

    ... to measure the speed of the nerve signals. Electromyography (recording from needles placed into the muscles) is ... Often, the nerve conduction test is followed by electromyography (EMG). In this test, needles are placed into ...

  15. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  16. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  17. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    ERIC Educational Resources Information Center

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  18. Aged adrenal medullary tissue survives intraocular grafting, forms nerve fibers and responds to nerve growth factor.

    PubMed

    Strömberg, I; Ebendal, T

    1989-06-01

    Adrenal medullary tissue from aged (24 months old) and young adult (2 months old) rats was grafted to the anterior chamber of the eye of previously sympathectomized animals. Nerve growth factor (NGF) was administered by weekly bilateral intraocular injections. Five weeks postgrafting, irides were prepared as whole mounts and processed for Falck-Hillarp histochemistry for visualization of catecholamines. NGF appeared to partially prevent the reduction in volume that both old and young grafts underwent. In the presence of NGF, an extensive, dense fiber network, closely resembling the normal adrenergic innervation, was formed in the host irides by grafts from aged donors. The area of outgrowth from aged transplants without NGF treatment was as large as with NGF treatment but less dense. The reinnervation of irides by NGF-treated young adult grafts occupied a similar area as that seen with aged grafts, but the pattern of innervation was irregular, particularly close to the transplants. Transplants from young adult donors without NGF treatment generated a sparse, limited network of nerves in the irides. All grafts were tyrosine hydroxylase-, adrenaline-, and dopamine-beta-hydroxylase-immunoreactive in about the same proportion of cells, but the grafts from the young donors were smaller in size. We concluded that the ability of chromaffin cells to transform toward a neuronal phenotype, produce nerve fibers, and respond to exogenous NGF is maintained in aged adrenals. PMID:2754763

  19. Adrenergic Metabolic and Hemodynamic Effects of Octopamine in the Liver

    PubMed Central

    de Oliveira, Andrea Luiza; de Paula, Mariana Nascimento; Comar, Jurandir Fernando; Vilela, Vanessa Rodrigues; Peralta, Rosane Marina; Bracht, Adelar

    2013-01-01

    The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite suppressants. A component of these extracts is octopamine, which is an adrenergic agent. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of octopamine on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways and hemodynamics. Octopamine increased glycogenolysis, glycolysis, oxygen uptake, gluconeogenesis and the portal perfusion pressure. Octopamine also accelerated the oxidation of exogenous fatty acids (octanoate and oleate), as revealed by the increase in 14CO2 production derived from 14C labeled precursors. The changes in glycogenolysis, oxygen uptake and perfusion pressure were almost completely abolished by α1-adrenergic antagonists. The same changes were partly sensitive to the β-adrenergic antagonist propranolol. It can be concluded that octopamine accelerates both catabolic and anabolic processes in the liver via adrenergic stimulation. Acceleration of oxygen uptake under substrate-free perfusion conditions also means acceleration of the oxidation of endogenous fatty acids, which are derived from lipolysis. All these effects are compatible with an overall stimulating effect of octopamine on metabolism, which is compatible with its reported weight-loss effects in experimental animals. PMID:24196353

  20. Adrenal medullary regulation of rat renal cortical adrenergic receptors

    SciTech Connect

    Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr. )

    1987-11-01

    The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of ({sup 3}H)prazosin, ({sup 3}H)rauwolscine, and ({sup 125}I)iodocyanopindolol were used to quantitate {alpha}{sub 1}-, {alpha}{sub 2}-, and {beta}-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B{sub max}, per milligram membrane protein) for {alpha}{sub 1}-, and {alpha}{sub 2}-, and {beta}-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K{sub D}) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine.

  1. Distal nerve entrapment following nerve repair.

    PubMed

    Schoeller, T; Otto, A; Wechselberger, G; Pommer, B; Papp, C

    1998-04-01

    Failure of nerve repair or poor functional outcome after reconstruction can be influenced by various causes. Besides improper microsurgical technique, fascicular malalignment and unphysiologic tension, we found in our clinical series that a subclinical nerve compression distal to the repair site can seriously impair regeneration. We concluded that the injured nerve, whether from trauma or microsurgical intervention, could be more susceptible to distal entrapment in the regenerative stage because of its disturbed microcirculation, swelling and the increase of regenerating axons followed by increased nerve volume. In two cases we found the regenerating nerve entrapped at pre-existing anatomical sites of narrowing resulting in impaired functional recovery. In both cases the surgical therapy was decompression of the distal entrapped nerve and this was followed by continued regeneration. Thorough clinical and electrophysiologic follow-up is necessary to detect such adverse compression effects and to distinguish between the various causes of failed regeneration. Under certain circumstances primary preventive decompression may be beneficial if performed at the time of nerve coaptation.

  2. Arthroscopic medial meniscus trimming or repair under nerve blocks: Which nerves should be blocked?

    PubMed Central

    Taha, AM; Abd-Elmaksoud, AM

    2016-01-01

    Background: This study aimed to determine the role of the sciatic and obturator nerve blocks (in addition to femoral block) in providing painless arthroscopic medial meniscus trimming/repair. Materials and Methods: One hundred and twenty patients with medial meniscus tear, who had been scheduled to knee arthroscopy, were planned to be included in this controlled prospective double-blind study. The patients were randomly allocated into three equal groups; FSO, FS, and FO. The femoral, sciatic, and obturator nerves were blocked in FSO groups. The femoral and sciatic nerves were blocked in FS group, while the femoral and obturator nerves were blocked in FO group. Intraoperative pain and its causative surgical maneuver were recorded. Results: All the patients (n = 7, 100%) in FO group had intraoperative pain. The research was terminated in this group but completed in FS and FSO groups (40 patients each). During valgus positioning of the knee for surgical management of the medial meniscus tear, the patients in FS group experienced pain more frequently than those in FSO group (P = 0.005). Conclusion: Adding a sciatic nerve block to the femoral nerve block is important for painless knee arthroscopy. Further adding of an obturator nerve block may be needed when a valgus knee position is required to manage the medial meniscus tear. PMID:27375382

  3. Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve.

    PubMed

    Terayama, Ryuji; Yamamoto, Yuya; Kishimoto, Noriko; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that peripheral nerve injury induced excessive nociceptive response of spinal cord dorsal horn neurons and such change has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the spinal dorsal horn for convergence of nociceptive input to second-order neurons deafferented by peripheral nerve injury. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input to spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and by electrical stimulation of the injured or uninjured saphenous nerve, respectively. Within the central terminal field of the saphenous nerve, the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was significantly decreased at 3 days and returned to the control level by 14 days after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed in the central terminal field of the saphenous nerve, and the topographic distribution pattern and number of such p-ERK-IR cell profiles remained unchanged after the nerve injury. The time course of changes in the number of double-labeled cell profiles was similar to that of c-Fos-IR cell profiles after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves contributes to increased responsiveness of spinal dorsal horn nociceptive neurons.

  4. Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs

    NASA Technical Reports Server (NTRS)

    Kiuchi, K.; Vatner, D. E.; Uemura, N.; Bigaud, M.; Hasebe, N.; Hempel, D. M.; Graham, R. M.; Vatner, S. F.

    1992-01-01

    To investigate the mechanisms of alpha 1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD) (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha 1-adrenergic agonist were significantly depressed (p < 0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the presence of beta-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5 versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs

  5. Adrenergic receptors on cerebral microvessels in control and Parkinsonian subjects

    SciTech Connect

    Cash, R.; Lasbennes, F.; Sercombe, R.; Seylaz, J.; Agid, Y.

    1985-08-12

    The binding of adrenergic ligands (/sup 3/H-prazosin, /sup 3/H-clonidine, /sup 3/H-dihydroalprenolol) was studied on a preparation of cerebral microvessels in the prefrontal cortex and putamen of control and Parkinsonian subjects. The adrenergic receptor density in microvessels of control patients was less than 0.5% and 3.3% respectively of the total binding. A significant decrease in the number of alpha-1 binding sites was observed on microvessels in the putamen of patients with Parkinson's disease. 22 references, 2 tables.

  6. Changes of lymphocyte beta-adrenergic receptors after surgical stress.

    PubMed

    Eandi, M; Buraglio, M; Arduino, C; Viano, I; Sansalvadore, G; Arbinolo, M A

    1984-01-01

    In this study the authors' purpose was to observe the effects of surgical stress on the number of lymphocyte beta-adrenergic receptors in hypertensive and normotensive subjects. It was noticed that after surgery a significant reduction occurred in the number of binding sites of lymphocytes of both hypertensive and normotensive subjects. The time course of recovery to the pre-operative values of binding sites varied between the two groups, being slower in normotensive than in hypertensive patients. This might suggest a different pattern of regulation of the beta-adrenergic receptor between hypertensive and normotensive subjects.

  7. Effect of adrenergic stimulation on cutaneous microcirculation immediately after surgical adventitiectomy in a rat skin flap model.

    PubMed

    Lecoq, Jean-Pierre H; Joris, Jean L; Nelissen, Xavier P; Lamy, Maurice L; Heymans, Olivier Y

    2008-01-01

    Chronic sympathetic denervation leads to the development of supersentivity to adrenergic agents. Free flap surgery results in the disruption of the autonomic nerve fibers running along the anastomosed vessels. We therefore investigated the early effect of surgical sympathectomy on the reactivity of cutaneous microcirculation challenged to adrenergic agents. Two epigastric flaps were elevated and exposed in 15 rats. On the right flap (Side A), a circular adventitiectomy of the feeder vessels was realized to provide surgical sympathectomy. On the left flap (Side N), vessels were kept intact. The following drugs were then given intravenously successively: phenylephrine (10 and 15 microg kg(-1)), norepinephrine (10 microg kg(-1)), prazocin (1 mg kg(-1)) followed by norepinephrine (10 microg kg(-1)). Cutaneous microcirculation was assessed using Laser-Doppler Flowmeters simultaneously on the two flaps after each drug administration. Mean arterial pressure was also measured. On side N, phenylephrine and norepinephrine resulted in a transient increase in cutaneous microcirculation followed by a more prolonged reduction. On side A, only the initial increase was observed, which was greater and longer as compared with side N, and paralleled the increase in mean arterial pressure. After prazocin pre-treatment, norepinephrine produced a transient increase in cutaneous microcirculation similar on both sides, and parallel to the changes in arterial pressure. No decrease in cutaneous microcirculation was observed. Immediately after surgical adventitiectomy, the vasoconstriction produced by alpha-adrenergic agents is prevented. No denervation-induced hypersentivity is observed. Surgical sympathectomy might protect cutaneous flaps from vasoconstriction induced by endogenous catecholamines release. PMID:18623150

  8. Bank Terminals

    NASA Technical Reports Server (NTRS)

    1978-01-01

    In the photo, employees of the UAB Bank, Knoxville, Tennessee, are using Teller Transaction Terminals manufactured by SCI Systems, Inc., Huntsville, Alabama, an electronics firm which has worked on a number of space projects under contract with NASA. The terminals are part of an advanced, computerized financial transaction system that offers high efficiency in bank operations. The key to the system's efficiency is a "multiplexing" technique developed for NASA's Space Shuttle. Multiplexing is simultaneous transmission of large amounts of data over a single transmission link at very high rates of speed. In the banking application, a small multiplex "data bus" interconnects all the terminals and a central computer which stores information on clients' accounts. The data bus replaces the maze-of wiring that would be needed to connect each terminal separately and it affords greater speed in recording transactions. The SCI system offers banks real-time data management through constant updating of the central computer. For example, a check is immediately cancelled at the teller's terminal and the computer is simultaneously advised of the transaction; under other methods, the check would be cancelled and the transaction recorded at the close of business. Teller checkout at the end of the day, conventionally a time-consuming matter of processing paper, can be accomplished in minutes by calling up a summary of the day's transactions. SCI manufactures other types of terminals for use in the system, such as an administrative terminal that provides an immediate printout of a client's account, and another for printing and recording savings account deposits and withdrawals. SCI systems have been installed in several banks in Tennessee, Arizona, and Oregon and additional installations are scheduled this year.

  9. Adrenergic regulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic theca-interstitial cell recognition sites.

    PubMed

    Hernandez, E R; Jimenez, J L; Payne, D W; Adashi, E Y

    1988-04-01

    Acting alone or in concert with pituitary gonadotropins, catecholamines have recently been shown to enhance androgen production by ovarian theca-interstitial cells. It is the objective of the in vitro studies reported herein to further characterize this catecholaminergic activity as well as to type and subtype the putative adrenergic recognition sites mediating this phenomenon. Treatment of collagenase-processed whole ovarian dispersates or highly enriched (greater than 90%) theca-interstitial cells from immature rats with norepinephrine (10(-6) M) resulted in a 2.0-fold increment in the accumulation of androsterone (3 alpha-hydroxy-5 alpha-androstane-17-one), the main androgenic steroid identified in culture medium by HPLC. Qualitatively similar stimulation was obtained using beta (isoproterenol)- but not alpha (methoxamine)-selective adrenergic agonists. Moreover, combined treatment with both norepinephrine (10(-6) M) and hCG (1 ng/ml) unmasked a synergistic interaction subject to stereospecific blockade by beta (propranolol)- but not alpha (phentolamine)-selective adrenergic antagonists. Further probing with subtype-selective adrenergic ligands revealed terbutaline (a beta 2-selective agonist) to enhance androgen biosynthesis, with dobutamine (a beta 1-selective agonist) having little or no effect. Moreover, a beta 2 (ICI-118406)- but not a beta 1 (ICI-89406)-selective adrenergic antagonist yielded dose-dependent inhibition of the isoproterenol effect. Unaccounted for by either enhanced cellular growth or an alteration of the overall steroidogenic pattern, catecholaminergically stimulated androgen biosynthesis proved time and dose dependent but independent of the hCG dose (0.1-10 ng/ml) employed. Binding of [125I]iodocyanopindolol to highly enriched theca-interstitial cells proved stereoselective and saturable, displaying a single class (Hill coefficient = 0.96 +/- 0.01) of high affinity (Kd = 5.6 X 10(-11) M), low capacity (1219 +/- 317 sites/cell) binding

  10. The Furcal Nerve Revisited

    PubMed Central

    Dabke, Harshad V.

    2014-01-01

    Atypical sciatica and discrepancy between clinical presentation and imaging findings is a dilemma for treating surgeon in management of lumbar disc herniation. It also constitutes ground for failed back surgery and potential litigations thereof. Furcal nerve (Furcal = forked) is an independent nerve with its own ventral and dorsal branches (rootlets) and forms a link nerve that connects lumbar and sacral plexus. Its fibers branch out to be part of femoral and obturator nerves in-addition to the lumbosacral trunk. It is most commonly found at L4 level and is the most common cause of atypical presentation of radiculopathy/sciatica. Very little is published about the furcal nerve and many are unaware of its existence. This article summarizes all the existing evidence about furcal nerve in English literature in an attempt to create awareness and offer insight about this unique entity to fellow colleagues/professionals involved in spine care. PMID:25317309

  11. Sympathetic Nervous System Control of Carbon Tetrachloride-Induced Oxidative Stress in Liver through α-Adrenergic Signaling.

    PubMed

    Lin, Jung-Chun; Peng, Yi-Jen; Wang, Shih-Yu; Lai, Mei-Ju; Young, Ton-Ho; Salter, Donald M; Lee, Herng-Sheng

    2016-01-01

    In addition to being the primary organ involved in redox cycling, the liver is one of the most highly innervated tissues in mammals. The interaction between hepatocytes and sympathetic, parasympathetic, and peptidergic nerve fibers through a variety of neurotransmitters and signaling pathways is recognized as being important in the regulation of hepatocyte function, liver regeneration, and hepatic fibrosis. However, less is known regarding the role of the sympathetic nervous system (SNS) in modulating the hepatic response to oxidative stress. Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma. Mice treated with 6-hydroxydopamine hydrobromide were used to realize chemical sympathectomy. Carbon tetrachloride (CCl4) injection was used to induce oxidative liver injury. Sympathectomized animals were protected from CCl4 induced hepatic lipid peroxidation-mediated cytotoxicity and genotoxicity as assessed by 4-hydroxy-2-nonenal levels, morphological features of cell damage, and DNA oxidative damage. Furthermore, sympathectomy modulated hepatic inflammatory response induced by CCl4-mediated lipid peroxidation. CCl4 induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist. We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.

  12. DNA encoding an. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Weinshank, R.L.; Hartig, P.R.

    1991-10-01

    This paper describes an isolated nucleic acid molecule encoding a human alpha 2B-adrenergic receptor. This patent also describes an isolated nucleic acid molecule, wherein the isolated nucleic acid molecule is a DNA molecule and a mammalian cell comprising the DNA molecule.

  13. Molecular characterization of an. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Harrison, J.K.; Dewan Zeng; D'Angelo, D.D.; Tucker, A.L.; Zhihong Lu; Barber, C.M.; Lynch, K.R. )

    1990-02-26

    {alpha}{sub 2}-Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNG{alpha}2) encoding a previously undescribed third subtype of an {alpha}{sub 2}-adrenergic receptor from a rat kidney cDNA library. The library was screened with an oligonucleotide encoding a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of G-protein coupled receptors with exception of the absence of the consensus N-linked glycosylation site at the amino terminus. Membranes prepared from COS-1 cells transfected with pRNG{alpha}2 display high affinity and saturable binding to {sup 3}H-rauwolscine (K{sub d}=2 nM).Competition curve data analysis shows that pRNG{alpha}2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine {ge} cholorpromazine > prazosin {ge} clonidine > norepinephrine {ge} oxymetazoline. pRNG{alpha}2 RNA accumulates in both adult rat kidney and rat neonatal lung (predominant species is 4.0 kb). They conclude that pRNG{alpha}2 likely represents a cDNA for the {alpha}{sub 2B}-adrenergic receptor.

  14. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  15. Cryotherapy and nerve palsy.

    PubMed

    Drez, D; Faust, D C; Evans, J P

    1981-01-01

    Ice application is one of the most extensively used treatments for athletic injuries. Frostbite is a recognized danger. Five cases of nerve palsy resulting from ice application are reported here. These palsies were temporary. They usually resolve spontaneously without any significant sequelae. This complication can be avoided by not using ice for more than 30 minutes and by guarding superficial nerves in the area.

  16. Imaging the cranial nerves.

    PubMed

    Parry, Andrew T; Volk, Holger A

    2011-01-01

    An understanding of the normal course of the cranial nerves (CN) is essential when interpreting images of patients with cranial neuropathies. CN foramina are depicted best using computed X-ray tomography, but the nerves are depicted best using magnetic resonance imaging. The function and anatomy of the CN in the dog are reviewed and selected examples of lesions affecting the CN are illustrated.

  17. [Sciatic nerve intraneural perineurioma].

    PubMed

    Bonhomme, Benjamin; Poussange, Nicolas; Le Collen, Philippe; Fabre, Thierry; Vital, Anne; Lepreux, Sébastien

    2015-12-01

    Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient. PMID:26586011

  18. Optic Nerve Decompression

    MedlinePlus

    ... canals). The optic nerve is the “nerve of vision” and extends from the brain, through your skull, and into your eye. A ... limited to, the following: loss of vision, double vision, inadequate ... leakage of brain fluid (CSF), meningitis, nasal bleeding, infection of the ...

  19. Ulnar nerve tuberculoma.

    PubMed

    Ramesh Chandra, V V; Prasad, Bodapati Chandramowliswara; Varaprasad, Gangumolu

    2013-01-01

    The authors report a very rare case of tuberculoma involving the ulnar nerve. The patient, a 7-year-old girl, presented with swelling over the medial aspect of her right forearm just below the elbow joint, with features of ulnar nerve palsy, including paresthesias along the little and ring fingers and claw hand deformity. There was a history of trauma and contact with a contagious case of tuberculosis. There were no other signs of tuberculosis. At surgical exploration the ulnar nerve was found to be thickened, and on opening the sheath there was evidence of caseous material enclosed in a fibrous capsule compressing and displacing the nerve fibers. The lesion, along with the capsule, was subtotally removed using curettage, and a part of the capsule that was densely adherent to the nerve fibers was left in the patient. Histopathological examination of the specimen was consistent with tuberculoma. The patient received adequate antitubercular treatment and showed significant improvement.

  20. Peripheral nerve stimulation: definition.

    PubMed

    Abejón, David; Pérez-Cajaraville, Juan

    2011-01-01

    Recently, there has been a tremendous evolution in the field of neurostimulation, both from the technological point of view and from development of the new and different indications. In some areas, such as peripheral nerve stimulation, there has been a boom in recent years due to the variations in the surgical technique and the improved results documented by in multiple published papers. All this makes imperative the need to classify and define the different types of stimulation that are used today. The confusion arises when attempting to describe peripheral nerve stimulation and subcutaneous stimulation. Peripheral nerve stimulation, in its pure definition, involves implanting a lead on a nerve, with the aim to produce paresthesia along the entire trajectory of the stimulated nerve.

  1. Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

    PubMed

    Kadow, Brian T; Lyon, Timothy D; Zhang, Zhaocun; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-07-01

    This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1-3 mg/kg iv) significantly (P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly (P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly (P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a β-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition. PMID:27170683

  2. Benign anatomical mistakes: the correct anatomical term for the recurrent laryngeal nerve.

    PubMed

    Mirilas, Petros; Skandalakis, John E

    2002-01-01

    The term recurrent laryngeal nerve has been adopted by Nomina Anatomica (1989) and Terminologia Anatomica (1998) to describe this vagus branch from its origin, its turn dorsally around the subclavian artery and the aortic arch, and its cranial pathway until it reaches its terminal organs in the neck. However, there is still much confusion, and either the terms inferior and recurrent laryngeal nerve are used interchangeably or inferior laryngeal nerve is considered the terminal branch of the recurrent laryngeal nerve. We hereby feel that it is necessary to reassess the term and we propose the term inferior laryngeal nerve for the entire nerve under consideration, from its origin from the vagus nerve to its destinations, including tracheal, esophageal, and pharyngeal branches. If the term superior laryngeal nerve is a given, standard and accepted term in the anatomical terminology, then logically the term inferior laryngeal nerve should also be accepted, as opposed to it. Of course the upward travel of the inferior laryngeal nerve is "recurrent". When nonrecurrence is encountered together with an arteria lusoria, a retroesophageal right subclavian artery or a right aortic arch, we consider that the term nonrecurrent inferior laryngeal nerve should be used to describe the deviation from the normal.

  3. Pharmacological Profiles of Alpha 2 Adrenergic Receptor Agonists Identified Using Genetically Altered Mice and Isobolographic Analysis

    PubMed Central

    Fairbanks, Carolyn A.; Stone, Laura S.; Wilcox, George L.

    2009-01-01

    Endogenous, descending noradrenergic fibers convey powerful analgesic control over spinal afferent circuitry mediating the rostrad transmission of pain signals. These fibers target alpha 2 adrenergic receptors (α2ARs) on both primary afferent terminals and secondary neurons, and their activation mediates substantial inhibitory control over this transmission, rivaling that of opioid receptors which share similar a similar pattern of distribution. The terminals of primary afferent nociceptive neurons and secondary spinal dorsal horn neurons express α2AAR and α2CAR subtypes, respectively. Spinal delivery of these agents serves to reduce their side effects, which are mediated largely at supraspinal sites, by concentrating the drugs at the spinal level. Targeting these spinal α2ARs with one of five selective therapeutic agonists, clonidine, dexmedetomidine, brimonidine, ST91 and moxonidine, produces significant antinociception that can work in concert with opioid agonists to yield synergistic antinociception. Application of several genetically altered mouse lines had facilitated identification of the primary receptor subtypes that likely mediate the antinociceptive effects of these agents. This review provides first an anatomical description of the localization of the three subtypes in the central nervous system, second a detailed account of the pharmacological history of each of these six primary agonists, and finally a comprehensive report of the specific interactions of other GPCR agonists with each of the six principal α2AR agonists featured. PMID:19393691

  4. Anabolic action of parathyroid hormone regulated by the β2-adrenergic receptor.

    PubMed

    Hanyu, Ryo; Wehbi, Vanessa L; Hayata, Tadayoshi; Moriya, Shuichi; Feinstein, Timothy N; Ezura, Yoichi; Nagao, Masashi; Saita, Yoshitomo; Hemmi, Hiroaki; Notomi, Takuya; Nakamoto, Tetsuya; Schipani, Ernestina; Takeda, Shu; Kaneko, Kazuo; Kurosawa, Hisashi; Karsenty, Gerard; Kronenberg, Henry M; Vilardaga, Jean-Pierre; Noda, Masaki

    2012-05-01

    Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the β(2)-adrenergic receptor (β(2)AR), respectively. These receptors activate a common cAMP/PKA signal transduction pathway mediated through the stimulatory heterotrimeric G protein. Activation of β(2)AR via the sympathetic nervous system decreases bone formation and increases bone resorption. Conversely, daily injection of PTH (1-34), a regimen known as intermittent (i)PTH treatment, increases bone mass through the stimulation of trabecular and cortical bone formation and decreases fracture incidences in severe cases of osteoporosis. Here, we show that iPTH has no osteoanabolic activity in mice lacking the β(2)AR. β(2)AR deficiency suppressed both iPTH-induced increase in bone formation and resorption. We showed that the lack of β(2)AR blocks expression of iPTH-target genes involved in bone formation and resorption that are regulated by the cAMP/PKA pathway. These data implicate an unexpected functional interaction between PTHR and β(2)AR, two G protein-coupled receptors from distinct families, which control bone formation and PTH anabolism. PMID:22538810

  5. Effects of serotonin and some other neurohumoral agents on adrenergic neurotransmission in spontaneously hypertensive rat vasculature.

    PubMed

    Kubo, T; Su, C

    1983-01-01

    The effects of serotonin (5HT), acetylcholine (ACh), histamine and dopamine on the pressor responses of the mesenteric vasculature were examined in view of their potential role in neuromodulation. The responses to periarterial sympathetic nerve stimulation (NS, 8 Hz, 2 msec, 30 sec) and to exogenous norepinephrine (NE, 0.2 nmol) were compared between spontaneously hypertensive rats (SHR) and the control Wistar Kyoto rats (WKY). In both WKY and SHR, ACh (3-30 nM), histamine (0.3-3 microM) and dopamine (0.3 microM) attenuated the NS-induced vasoconstrictor response as much as the NE-induced response, indicative of predominance of postsynaptic inhibition. 5HT (10-100 nM) potentiated the vasoconstrictor responses to NS significantly less than that to NE in WKY, suggestive of presynaptic inhibition. Such difference was absent in SHR. These results suggest that the presynaptic inhibition of vascular adrenergic neurotransmission by 5HT is diminished in SHR, and this may contribute to the elevated blood pressure.

  6. Terminal structure

    DOEpatents

    Schmidt, Frank; Allais, Arnaud; Mirebeau, Pierre; Ganhungu, Francois; Lallouet, Nicolas

    2009-10-20

    A terminal structure (2) for a superconducting cable (1) is described. It consists of a conductor (2a) and an insulator (2b) that surrounds the conductor (2a), wherein the superconducting cable (1) has a core with a superconducting conductor (5) and a layer of insulation that surrounds the conductor (5), and wherein the core is arranged in such a way that it can move longitudinally in a cryostat. The conductor (2a) of the terminal structure (2) is electrically connected with the superconducting conductor (5) or with a normal conductor (6) that is connected with the superconducting conductor (5) by means of a tubular part (7) made of an electrically conductive material, wherein the superconducting conductor (5) or the normal conductor (6) can slide in the part (7) in the direction of the superconductor.

  7. Termination unit

    DOEpatents

    Traeholt, Chresten; Willen, Dag; Roden, Mark; Tolbert, Jerry C.; Lindsay, David; Fisher, Paul W.; Nielsen, Carsten Thidemann

    2016-05-03

    Cable end section comprises end-parts of N electrical phases/neutral, and a thermally-insulation envelope comprising cooling fluid. The end-parts each comprises a conductor and are arranged with phase 1 innermost, N outermost surrounded by the neutral, electrical insulation being between phases and N and neutral. The end-parts comprise contacting surfaces located sequentially along the longitudinal extension of the end-section. A termination unit has an insulating envelope connected to a cryostat, special parts at both ends comprising an adapter piece at the cable interface and a closing end-piece terminating the envelope in the end-section. The special parts houses an inlet and/or outlet for cooling fluid. The space between an inner wall of the envelope and a central opening of the cable is filled with cooling fluid. The special part at the end connecting to the cryostat houses an inlet or outlet, splitting cooling flow into cable annular flow and termination annular flow.

  8. Histomorphogenesis of cranial nerves in Huso huso larvae

    PubMed Central

    Tavighi, Sherma; Saadatfar, Zohreh; Shojaei, Bahador; Behnam Rassouli, Morteza

    2016-01-01

    In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed. PMID:27482355

  9. Histomorphogenesis of cranial nerves in Huso huso larvae.

    PubMed

    Tavighi, Sherma; Saadatfar, Zohreh; Shojaei, Bahador; Behnam Rassouli, Morteza

    2016-01-01

    In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed. PMID:27482355

  10. Histomorphogenesis of cranial nerves in Huso huso larvae.

    PubMed

    Tavighi, Sherma; Saadatfar, Zohreh; Shojaei, Bahador; Behnam Rassouli, Morteza

    2016-01-01

    In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed.

  11. Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease.

    PubMed

    Hardwick, Jean C; Southerland, E Marie; Girasole, Allison E; Ryan, Shannon E; Negrotto, Sara; Ardell, Jeffrey L

    2012-11-01

    Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (∼20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg(-1)·day(-1)) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that β-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the β-receptors were more influential on remodeling during dynamic disease progression.

  12. Intraparotid facial nerve neurofibroma.

    PubMed

    Sullivan, M J; Babyak, J W; Kartush, J M

    1987-02-01

    Neurogenic neoplasms of the intraparotid facial nerve are uncommon and are usually diagnosed intraoperatively by tissue biopsy. Fifty-six cases of primary neurogenic neoplasms involving the facial nerve have been reported. The majority of these have been schwannomas. A case of a solitary neurofibroma involving the main trunk of the facial nerve is presented. Schwannomas and neurofibromas have distinct histological features which must be considered prior to the management of these tumors. The management of neurogenic tumors associated with normal facial function is a particularly difficult problem. A new approach for the diagnosis and management of neurogenic neoplasms is described utilizing electroneurography. PMID:3807626

  13. Radial Nerve Tendon Transfers.

    PubMed

    Cheah, Andre Eu-Jin; Etcheson, Jennifer; Yao, Jeffrey

    2016-08-01

    Radial nerve palsy typically occurs as a result of trauma or iatrogenic injury and leads to the loss of wrist extension, finger extension, thumb extension, and a reduction in grip strength. In the absence of nerve recovery, reconstruction of motor function involves tendon transfer surgery. The most common donor tendons include the pronator teres, wrist flexors, and finger flexors. The type of tendon transfer is classified based on the donor for the extensor digitorum communis. Good outcomes have been reported for most methods of radial nerve tendon transfers as is typical for positional tendon transfers not requiring significant power. PMID:27387076

  14. The effect of adrenergic blockade on blushing and facial flushing.

    PubMed

    Drummond, P D

    1997-03-01

    The effect of adrenergic blockade on vascular responses in the forehead was assessed during stressful mental arithmetic, singing, and moderate exercise in 21 frequent blushers and 21 infrequent blushers. Adrenergic antagonists were introduced into a small site on the forehead by iontophoresis, and vascular responses were monitored bilaterally with laser Doppler flowmetry. Beta blockade prevented increases in blood flow in infrequent blushers during mental arithmetic and partially inhibited vasodilatation during singing, indicating minor participation of beta-adrenoceptors in blushing. Alpha blockade did not affect blushing but augmented vasodilatation during exercise. Despite higher ratings of self-consciousness in frequent than in infrequent blushers, vascular responses were similar in both groups. Thus, blushing propensity does not appear to be related to the density of alpha- or beta-adrenoceptors in facial vessels and may have a psychological basis. PMID:9090265

  15. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  16. Beta 2-adrenergic receptors are colocalized and coregulated with "whisker barrels" in rat somatosensory cortex.

    PubMed Central

    Vos, P; Kaufmann, D; Hand, P J; Wolfe, B B

    1990-01-01

    Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-Adrenergic receptors, but not beta 1-adrenergic receptors colocalize with "whisker barrels" in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array. Images PMID:2164222

  17. Adrenergic and noradrenergic regulation of poultry behavior and production.

    PubMed

    Dennis, R L

    2016-07-01

    Norepinephrine and epinephrine (noradrenaline and adrenaline) are integral in maintaining behavioral and physiological homeostasis during both aversive and rewarding events. They regulate the response to stressful stimuli through direct activation of adrenergic receptors in the central and sympathetic nervous systems, hormonal activity and through the interaction of the brain, gut, and microbiome. The multiple functions of these catecholamines work synergistically to prepare an individual for a "fight or flight" response. However, hyper-reactivity of this system can lead to increased fearfulness and aggression, decreased health and productivity, and a reduction in overall well-being. Behaviors, such as aggression and certain fear-related behaviors, are a serious problem in the poultry industry that can lead to injury and cannibalism. For decades, catecholamines have been used as a measure of stress in animals. However, few studies have specifically targeted the adrenergic systems as means to reduce behaviors that are damaging or maladapted to their rearing environments and improve animal well-being. This article attempts to address our current understanding of specific, adrenergic-regulated behaviors that impact chicken well-being and production. PMID:27345328

  18. Facial Nerve Neuroma Management

    PubMed Central

    Weber, Peter C.; Osguthorpe, J. David

    1998-01-01

    Three facial nerve neuromas were identified in the academic year 1994-1995. Each case illustrates different management dilemmas. One patient with a grade III facial nerve palsy had a small geniculate ganglion neuroma with the dilemma of decompression versus resection clear nerve section margins. The second patient underwent facial neuroma resection with cable graft reconstruction, but the permanent sections were positive. The last patient had a massive neuroma in which grafting versus other facial reconstructive options were considered. These three cases illustrate some of the major controversies in facial nerve neuroma management. We discuss our decision-making plan and report our results. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:17171043

  19. Diabetes and nerve damage

    MedlinePlus

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  20. Vagus Nerve Stimulation

    PubMed Central

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  1. Sacral nerve stimulation.

    PubMed

    Matzel, K E; Stadelmaier, U; Besendörfer, M

    2004-01-01

    The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  2. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  3. Damaged axillary nerve (image)

    MedlinePlus

    Conditions associated with axillary nerve dysfunction include fracture of the humerus (upper arm bone), pressure from casts or splints, and improper use of crutches. Other causes include systemic disorders that cause neuritis (inflammation of ...

  4. Iatrogenic accessory nerve injury.

    PubMed Central

    London, J.; London, N. J.; Kay, S. P.

    1996-01-01

    Accessory nerve injury produces considerable disability. The nerve is most frequently damaged as a complication of radical neck dissection, cervical lymph node biopsy and other surgical procedures. The problem is frequently compounded by a failure to recognise the error immediately after surgery when surgical repair has the greatest chance of success. We present cases which outline the risk of accessory nerve injury, the spectrum of clinical presentations and the problems produced by a failure to recognise the deficit. Regional anatomy, consequences of nerve damage and management options are discussed. Diagnostic biopsy of neck nodes should not be undertaken as a primary investigation and, when indicated, surgery in this region should be performed by suitably trained staff under well-defined conditions. Awareness of iatrogenic injury and its consequences would avoid delays in diagnosis and treatment. Images Figure 2 PMID:8678450

  5. Femoral nerve dysfunction

    MedlinePlus

    Neuropathy - femoral nerve; Femoral neuropathy ... Craig EJ, Clinchot DM. Femoral neuropathy. In: Frontera WR, Silver JK, Rizzo TD Jr, eds. Essentials of Physical Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation . 3rd ...

  6. Diabetic Nerve Problems

    MedlinePlus

    ... the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...

  7. Lower cranial nerves.

    PubMed

    Soldatos, Theodoros; Batra, Kiran; Blitz, Ari M; Chhabra, Avneesh

    2014-02-01

    Imaging evaluation of cranial neuropathies requires thorough knowledge of the anatomic, physiologic, and pathologic features of the cranial nerves, as well as detailed clinical information, which is necessary for tailoring the examinations, locating the abnormalities, and interpreting the imaging findings. This article provides clinical, anatomic, and radiological information on lower (7th to 12th) cranial nerves, along with high-resolution magnetic resonance images as a guide for optimal imaging technique, so as to improve the diagnosis of cranial neuropathy.

  8. Characterization of a panel of six β2-adrenergic receptor antibodies by indirect immunofluorescence microscopy

    PubMed Central

    Koryakina, Yulia A; Fowler, Tristan W; Jones, Stacie M; Schnackenberg, Bradley J; Cornett, Lawrence E; Kurten, Richard C

    2008-01-01

    Background The β2-adrenergic receptor (β2AR) is a primary target for medications used to treat asthma. Due to the low abundance of β2AR, very few studies have reported its localization in tissues. However, the intracellular location of β2AR in lung tissue, especially in airway smooth muscle cells, is very likely to have a significant impact on how the airways respond to β-agonist medications. Thus, a method for visualizing β2AR in tissues would be of utility. The purpose of this study was to develop an immunofluorescent labeling technique for localizing native and recombinant β2AR in primary cell cultures. Methods A panel of six different antibodies were evaluated in indirect immunofluorescence assays for their ability to recognize human and rat β2AR expressed in HEK 293 cells. Antibodies capable of recognizing rat β2AR were identified and used to localize native β2AR in primary cultures of rat airway smooth muscle and epithelial cells. β2AR expression was confirmed by performing ligand binding assays using the β-adrenergic antagonist [3H] dihydroalprenolol ([3H]DHA). Results Among the six antibodies tested, we identified three of interest. An antibody developed against the C-terminal 15 amino acids of the human β2AR (Ab-Bethyl) specifically recognized human but not rat β2AR. An antibody developed against the C-terminal domain of the mouse β2AR (Ab-sc570) specifically recognized rat but not human β2AR. An antibody developed against 78 amino acids of the C-terminus of the human β2AR (Ab-13989) was capable of recognizing both rat and human β2ARs. In HEK 293 cells, the receptors were predominantly localized to the cell surface. By contrast, about half of the native rat β2AR that we visualized in primary cultures of rat airway epithelial and smooth muscle cells using Ab-sc570 and Ab-13989 was found inside cells rather than on their surface. Conclusion Antibodies have been identified that recognize human β2AR, rat β2AR or both rat and human β2AR

  9. Effect of conventional (mixed beta 1/beta 2) and novel (beta 3) adrenergic agonists on thermoregulatory behavior.

    PubMed

    Carlisle, H J; Stock, M J

    1991-10-01

    The effects of submaximal and maximal thermogenic doses of isoproterenol (ISO) on operant thermoregulatory responses in a cold (-8 degrees C) environment were tested in lean (+/?) Zucker rats trained to barpress for radiant heat. Contrary to expectations, ISO rats pressed for twice as much exogenous heat as controls, but showed a smaller rise in colonic temperature. Conversely, a beta 3-selective adrenergic agonist (RO40-2148) decreased the requirement for exogenous heat and produced larger rises in colonic temperature. RO40-2148 and another beta 3-agonist (ICI D7114) produced similar responses in obese (fa/fa) Zucker rats, but tests with ISO were terminated because it caused profound, and lethal hypothermia. The hypothermic effects of ISO on colonic temperature were also observed in Sprague-Dawley rats at room temperature (22 degrees C), whereas RO40-2148 produced hyperthermia. These results provide behavioral evidence for the high thermogenic selectivity of these novel adrenergic agonists and support the existence of an atypical beta 3-adrenoceptor. The hypothermic effects of ISO are presumed to be due to actions on beta 1- and/or beta 2-adrenoceptors. PMID:1687163

  10. The Role of Alpha-2 Adrenergic Receptors in Anti-ulcer Activity.

    PubMed

    Suleyman, Halis

    2012-04-01

    Although peptic ulcer disease has long been recognized, the proposed mechanisms of its etiopathogenesis change every year. This review shows that gastric ulcers have a significant relationship with alpha-2 adrenergic receptors. The aggravating factors of gastric ulcer formation have been reported to act by blocking alpha-2 adrenergic receptors, whereas drugs possessing anti-ulcer activity have been shown to ensure gastric protection by stimulating the alpha-2 adrenergic receptors. The data derived from the literature indicate the likelihood that any drug or substance selectively stimulating the alpha-2 adrenergic receptors may possess anti-ulcer activity.

  11. β2-adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis

    PubMed Central

    Jiao, Kai; Niu, Li-Na; Li, Qi-hong; Ren, Gao-tong; Zhao, Chang-ming; Liu, Yun-dong; Tay, Franklin R.; Wang, Mei-qing

    2015-01-01

    The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs. PMID:26219508

  12. β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.

    PubMed

    Jiao, Kai; Niu, Li-Na; Li, Qi-hong; Ren, Gao-tong; Zhao, Chang-ming; Liu, Yun-dong; Tay, Franklin R; Wang, Mei-qing

    2015-07-29

    The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.

  13. [Antifibrillatory activity of dipeptide antagonist of nerve growth factor].

    PubMed

    Kryzhanovskiĭ, S A; Stoliarchuk, V N; Vititnova, M B; Tsorin, I B; Pekel'dina, E S; Gudasheva, T A

    2012-01-01

    In experiments on anesthetized rats were assessed antifibrillatoty action of dipeptide GK-1. This compound is the fragment of fourth loop of nerve growth factor (NGF) and manifests antagonistic activity in respect to TrkA receptor, that specified for NGF. It is shown that this compound is able to significantly increase the threshold of electrical fibrillation of the heart and its effectiveness is not inferior to the reference antiarrhythmics I and III class on Vaughan Williams classification. However, unlike the latter, antifibrillatory action of dipeptide GK-1 was delayed and realized within 40-60 minutes after its administration. It is discussed possible mechanisms underlying antifibrillatory action of dipeptide GK-1, that, to some extent, may be associated with its ability to change the reactivity of beta-adrenergic structures of the heart.

  14. Communications Between the Facial Nerve and the Vestibulocochlear Nerve, the Glossopharyngeal Nerve, and the Cervical Plexus.

    PubMed

    Hwang, Kun; Song, Ju Sung; Yang, Su Cheol

    2015-10-01

    The aim of this review is to elucidate the communications between the facial nerves or facial nerve and neighboring nerves: the vestibulocochlear nerve, the glossopharyngeal nerve, and the cervical plexus.In a PubMed search, 832 articles were searched using the terms "facial nerve and communication." Sixty-two abstracts were read and 16 full-text articles were reviewed. Among them, 8 articles were analyzed.The frequency of communication between the facial nerve and the vestibulocochlear nerve was the highest (82.3%) and the frequency of communication between the facial nerve and the glossopharyngeal nerve was the lowest (20%). The frequency of communication between the facial nerve and the cervical plexus was 65.2 ± 43.5%. The frequency of communication between the cervical branch and the marginal mandibular branch of the facial nerve was 24.7 ± 1.7%.Surgeons should be aware of the nerve communications, which are important during clinical examinations and surgical procedures of the facial nerves such as those communications involved in facial reconstructive surgery, neck dissection, and various nerve transfer procedures.

  15. Peripheral communications of intercostobrachial nerve Peripheral communications of the intercostobrachial nerve in relation to the alar thoracic artery

    PubMed Central

    Rustagi, Shaifaly Madan; Sharma, Mona; Singh, Nidhi; Mehta, Vandana; Suri, Rajesh K; Rath, Gayatri

    2015-01-01

    The intercostobrachial nerve (ICBN) is often encountered during axillary dissection for axillary lymph node dissection (ALND) for diagnostic and therapeutic surgery for mastectomy. The present report is a case observed in the Department of Anatomy at Vardhman Mahavir Medical College, Delhi during routine dissection of the upper extremity of a male cadaver for first year undergraduate medical students. On the right side, the medial cord of brachial plexus gave two medial cutaneous nerves of arm. Both the nerves were seen communicating with the branches of the ICBN. The ICBN and one of its branches were surrounding the termination of an alar thoracic artery. These peripheral neural connections of the ICBN with the branches of the medial cord can be a cause of sensory impairment during axillary procedures done for mastectomy or exploration of long thoracic nerves. The alar thoracic artery found in relation to the ICBN could further be a cause of vascular complications during such procedures. PMID:25802820

  16. Peripheral communications of intercostobrachial nerve Peripheral communications of the intercostobrachial nerve in relation to the alar thoracic artery.

    PubMed

    Rustagi, Shaifaly Madan; Sharma, Mona; Singh, Nidhi; Mehta, Vandana; Suri, Rajesh K; Rath, Gayatri

    2015-01-01

    The intercostobrachial nerve (ICBN) is often encountered during axillary dissection for axillary lymph node dissection (ALND) for diagnostic and therapeutic surgery for mastectomy. The present report is a case observed in the Department of Anatomy at Vardhman Mahavir Medical College, Delhi during routine dissection of the upper extremity of a male cadaver for first year undergraduate medical students. On the right side, the medial cord of brachial plexus gave two medial cutaneous nerves of arm. Both the nerves were seen communicating with the branches of the ICBN. The ICBN and one of its branches were surrounding the termination of an alar thoracic artery. These peripheral neural connections of the ICBN with the branches of the medial cord can be a cause of sensory impairment during axillary procedures done for mastectomy or exploration of long thoracic nerves. The alar thoracic artery found in relation to the ICBN could further be a cause of vascular complications during such procedures.

  17. Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in Experimental Pulmonary Artery Hypertension.

    PubMed

    Zhao, Qingyan; Deng, Hongping; Jiang, Xuejun; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Hu, Wei; Yu, Shengbo; Yang, Bo; Tang, Yanhong; Huang, Congxin

    2015-11-01

    Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter (AFL), is common in patients with pulmonary arterial hypertension (PAH), who often have increased sympathetic nerve activity. Here, we tested the hypothesis that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The atrial effective refractory period and AF/AFL inducibility at baseline and after anterior right ganglionated plexi ablation were determined during left stellate ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs with or without PAH. Then, sympathetic nerve, β-adrenergic receptor densities and connexin 43 expression in atrial tissues were assessed. The sum of the window of vulnerability to AF/AFL was increased in the right atrium compared with the left atrium at baseline in the PAH dogs but not in the controls. The atrial effective refractory period dispersion was increased in the control dogs, but not in the PAH dogs, during left stellate ganglion stimulation. The voltage thresholds for inducing AF/AFL during anterior right ganglionated plexi stimulation were lower in the PAH dogs than in the controls. The AF/AFL inducibility was suppressed after ablation of the anterior right ganglionated plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and β1-adrenergic receptor densities, increased levels of nonphosphorylated connexin 43, and heterogeneous connexin 43 expression in the right atrium when compared with the control dogs. The anterior right ganglionated plexi play important roles in the induction of AF/AFL. AF/AFL induction was associated with right atrium substrate remodeling in dogs with PAH.

  18. Molecular and pharmacological characteristics of the gerbil α(1a)-adrenergic receptor.

    PubMed

    Witt, Kelly M; Bockman, Charles S; Dang, Herbert K; Gruber, Daniel D; Wangemann, Philine; Scofield, Margaret A

    2012-01-01

    The spiral modiolar artery supplies blood and essential nutrients to the cochlea. Our previous functional study indicates the α(1A)-adrenergic receptor subtype mediates vasoconstriction of the gerbil spiral modiolar artery. Although the gerbil cochlea is often used as a model in hearing research, the molecular and pharmacological characteristics of the cloned gerbil α(1a)-adrenergic receptor have not been determined. Thus we cloned, expressed and characterized the gerbil α(1a)-adrenergic receptor and then compared its molecular and pharmacological properties to those of other mammalian α(1a)-adrenergic receptors. The cDNA clone contained 1404 nucleotides, which encoded a 467 amino acid peptide with a deduced sequence having 96.8, 96.4 and 91.6% identity to rat, mouse and human α(1a)-receptors, respectively. We transiently transfected the α(1a)-adrenergic receptor into COS-1 cells and determined its pharmacological characteristics by [(3)H]prazosin binding. Unlabeled prazosin had a K(i) of 0.89±0.1nM. The α(1A)-adrenergic receptor-selective antagonists, 5-methylurapidil and WB-4101, bound with high affinity and had K(i) values of 4.9±1 and 1.0±0.1nM, respectively. BMY-7378, an α(1D)-adrenergic receptor-selective antagonist, bound with low affinity (260±60nM). The 91.6% amino acid sequence identity and K(i)s of the cloned gerbil α(1a)-adrenergic receptor are similar to those of the human α(1a)-adrenergic receptor clone. These results show that the gerbil α(1a)-adrenergic receptor is representative of the human α(1a)-adrenergic receptor, lending validity to the use of the gerbil spiral modiolar artery as a model in studies of vascular disorders of the cochlea.

  19. Regulation of subtypes of beta-adrenergic receptors in rat brain following treatment with 6-hydroxydopamine

    SciTech Connect

    Johnson, E.W.; Wolfe, B.B.; Molinoff, P.B.

    1989-07-01

    The technique of quantitative autoradiography has been used to localize changes in the densities of subtypes of beta-adrenergic receptors in rat brain following treatment with 6-hydroxydopamine. Previously reported increases in the density of beta 1-adrenergic receptors in the cerebral cortex were confirmed. The anatomical resolution of autoradiography made it possible to detect changes in the density of beta 2-adrenergic receptors in the cortex and in a number of other brain regions. The density of beta 1-adrenergic receptors increased from 30 to 50% depending on the region of the cortex being examined. The increase in the somatomotor cortex was greater than that in the frontal or occipital cortex. The increase in the density of beta 2-adrenergic receptors in the cortex was not as widespread as that of beta 1-adrenergic receptors and occurred primarily in frontal cortex, where the density of receptors increased by 40%. The densities of both beta 1- and beta 2-adrenergic receptors increased in a number of forebrain, thalamic, and midbrain structures. Selective changes in the density of beta 1-adrenergic receptors were observed in the superficial gray layer of the superior colliculus and in the amygdala. The density of beta 2-adrenergic receptors increased in the caudate-putamen, the substantia nigra, and the lateral and central nuclei of the thalamus, whereas the density of beta 1-adrenergic receptors did not change in these regions. The densities of both subtypes of beta-adrenergic receptors increased in the hippocampus, the cerebellum, the lateral posterior nucleus of the thalamus, and the dorsal lateral geniculate.

  20. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    PubMed Central

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  1. Localization of cholecystokinin-like immunoreactivity in isolated nerve terminals.

    PubMed Central

    Pinget, M; Straus, E; Yalow, R S

    1978-01-01

    Subcellular fractionation of the rat cerebral cortex demonstrated the presence of immunoreactive cholecystokinin in the pellet identified by electron microscopy as containing a high proportion of synaptic vesicles. The recovery in this pellet of 40% of the total immunoreactivity in the initial cortical extract is quite comparable to the recovery of other peptides such as vasoactive intestinal polypeptide and somatostatin, which are also located in synaptosomes and for which roles as neuroregulators or transmitters have been suggested. The evidence of concentration of cholecystokinin-like peptides in the synaptosomal pellet is consistent with our earlier demonstration by immunohistochemical techniques of cholecystokinin's presence in rabbit cerebral cortical neurons. These observations and the evidence for diminished concentration of cholecystokinin-like peptides in the brains of hyperphagic mice are consistent with cholecystolinin's suggested role as a neuroregulator for appetite. Images PMID:282649

  2. Neuromuscular ultrasound of cranial nerves.

    PubMed

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  3. Axonal transport disruption in peripheral nerve disease

    PubMed Central

    Lloyd, Thomas E.

    2015-01-01

    Many neurodegenerative diseases and neuropathies have been proposed to be caused by a disruption of axonal transport. However, the mechanisms whereby impaired transport causes disease remain unclear. Proposed mechanisms include impairment in delivery of organelles such as mitochondria, defective retrograde neurotrophic signaling, and disruption of the synaptic vesicle cycle within the synaptic terminal. Simple model organisms such as the fruitfly, Drosophila melanogaster, allow live imaging of axonal transport to be combined with high-throughput genetic screens and are providing insights into the pathophysiology of peripheral nerve diseases. PMID:23279432

  4. Adrenergic signaling and oxidative stress: a role for sirtuins?

    PubMed Central

    Corbi, Graziamaria; Conti, Valeria; Russomanno, Giusy; Longobardi, Giancarlo; Furgi, Giuseppe; Filippelli, Amelia; Ferrara, Nicola

    2013-01-01

    The adrenergic system plays a central role in stress signaling and stress is often associated with increased production of ROS. However, ROS overproduction generates oxidative stress, that occurs in response to several stressors. β-adrenergic signaling is markedly attenuated in conditions such as heart failure, with downregulation and desensitization of the receptors and their uncoupling from adenylyl cyclase. Transgenic activation of β2-adrenoceptor leads to elevation of NADPH oxidase activity, with greater ROS production and p38MAPK phosphorylation. Inhibition of NADPH oxidase or ROS significantly reduced the p38MAPK signaling cascade. Chronic β2-adrenoceptor activation is associated with greater cardiac dilatation and dysfunction, augmented pro-inflammatory and profibrotic signaling, while antioxidant treatment protected hearts against these abnormalities, indicating ROS production to be central to the detrimental signaling of β2-adrenoceptors. It has been demonstrated that sirtuins are involved in modulating the cellular stress response directly by deacetylation of some factors. Sirt1 increases cellular stress resistance, by an increased insulin sensitivity, a decreased circulating free fatty acids and insulin-like growth factor (IGF-1), an increased activity of AMPK, increased activity of PGC-1a, and increased mitochondrial number. Sirt1 acts by involving signaling molecules such P-I-3-kinase-Akt, MAPK and p38-MAPK-β. βAR stimulation antagonizes the protective effect of the AKT pathway through inhibiting induction of Hif-1α and Sirt1 genes, key elements in cell survival. More studies are needed to better clarify the involvement of sirtuins in the β-adrenergic response and, overall, to better define the mechanisms by which tools such as exercise training are able to counteract the oxidative stress, by both activation of sirtuins and inhibition of GRK2 in many cardiovascular conditions and can be used to prevent or treat diseases such as heart failure

  5. Termination unit

    DOEpatents

    Traeholt, Chresten [Frederiksberg, DK; Willen, Dag [Klagshamn, SE; Roden, Mark [Newnan, GA; Tolbert, Jerry C [Carrollton, GA; Lindsay, David [Carrollton, GA; Fisher, Paul W [Heiskell, TN; Nielsen, Carsten Thidemann [Jaegerspris, DK

    2014-01-07

    This invention relates to a termination unit comprising an end-section of a cable. The end section of the cable defines a central longitudinal axis and comprising end-parts of N electrical phases, an end-part of a neutral conductor and a surrounding thermally insulation envelope adapted to comprising a cooling fluid. The end-parts of the N electrical phases and the end-part of the neutral conductor each comprising at least one electrical conductor and being arranged in the cable concentrically around a core former with a phase 1 located relatively innermost, and phase N relatively outermost in the cable, phase N being surrounded by the neutral conductor, electrical insulation being arrange between neighboring electrical phases and between phase N and the neutral conductor, and wherein the end-parts of the neutral conductor and the electrical phases each comprise a contacting surface electrically connected to at least one branch current lead to provide an electrical connection: The contacting surfaces each having a longitudinal extension, and being located sequentially along the longitudinal extension of the end-section of the cable. The branch current leads being individually insulated from said thermally insulation envelope by individual electrical insulators.

  6. Crystal structure of the β2 adrenergic receptor-Gs protein complex

    SciTech Connect

    Rasmussen, Søren G.F.; DeVree, Brian T; Zou, Yaozhong; Kruse, Andrew C; Chung, Ka Young; Kobilka, Tong Sun; Thian, Foon Sun; Chae, Pil Seok; Pardon, Els; Calinski, Diane; Mathiesen, Jesper M; Shah, Syed T.A.; Lyons, Joseph A; Caffrey, Martin; Gellman, Samuel H; Steyaert, Jan; Skiniotis, Georgios; Weis, William I; Sunahara, Roger K; Kobilka, Brian K

    2011-12-07

    G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β2 adrenergic receptor (β2AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β2AR and nucleotide-free Gs heterotrimer. The principal interactions between the β2AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β2AR include a 14Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.

  7. Mapping Neuronal Activation and the Influence of Adrenergic Signaling during Contextual Memory Retrieval

    ERIC Educational Resources Information Center

    Zhang, Wei-Ping; Guzowski, John F.; Thomas, Steven A.

    2005-01-01

    We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene "Arc" was used in…

  8. Antagonism of Lateral Amygdala Alpha1-Adrenergic Receptors Facilitates Fear Conditioning and Long-Term Potentiation

    ERIC Educational Resources Information Center

    Lazzaro, Stephanie C.; Hou, Mian; Cunha, Catarina; LeDoux, Joseph E.; Cain, Christopher K.

    2010-01-01

    Norepinephrine receptors have been studied in emotion, memory, and attention. However, the role of alpha1-adrenergic receptors in fear conditioning, a major model of emotional learning, is poorly understood. We examined the effect of terazosin, an alpha1-adrenergic receptor antagonist, on cued fear conditioning. Systemic or intra-lateral amygdala…

  9. Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

    PubMed

    Femminella, Grazia D; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2016-01-01

    The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID:27189470

  10. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting.

    PubMed

    Fernandez, Stanley F; Ovchinnikov, Vladislav; Canty, John M; Fallavollita, James A

    2013-01-15

    Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (-32%, P < 0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.

  11. α-1 Adrenergic receptors are localized on presynaptic elements in the nucleus accumbens and regulate mesolimbic dopamine transmission.

    PubMed

    Mitrano, Darlene A; Schroeder, Jason P; Smith, Yoland; Cortright, James J; Bubula, Nancy; Vezina, Paul; Weinshenker, David

    2012-08-01

    Brainstem noradrenergic neurons innervate the mesocorticolimbic reward pathway both directly and indirectly, with norepinephrine facilitating dopamine (DA) neurotransmission via α1-adrenergic receptors (α1ARs). Although α1AR signaling in the prefrontal cortex (PFC) promotes mesolimbic transmission and drug-induced behaviors, the potential contribution of α1ARs in other parts of the pathway, such as the ventral tegmental area (VTA) and nucleus accumbens (NAc), has not been investigated before. We found that local blockade of α1ARs in the medial NAc shell, but not the VTA, attenuates cocaine- and morphine-induced locomotion. To determine the neuronal substrates that could mediate these effects, we analyzed the cellular, subcellular, and subsynaptic localization of α1ARs and characterized the chemical phenotypes of α1AR-containing elements within the mesocorticolimbic system using single and double immunocytochemical methods at the electron microscopic (EM) level. We found that α1ARs are found mainly extra-synaptically in axons and axon terminals in the NAc and are enriched in glutamatergic and dopaminergic elements. α1ARs are also abundant in glutamatergic terminals in the PFC, and in GABA-positive terminals in the VTA. In line with these observations, microdialysis experiments revealed that local blockade of α1ARs attenuated the increase in extracellular DA in the medial NAc shell following administration of cocaine. These data indicate that local α1ARs control DA transmission in the medial NAc shell and behavioral responses to drugs of abuse.

  12. Phospholemman is a negative feed-forward regulator of Ca2+ in β-adrenergic signaling, accelerating β-adrenergic inotropy.

    PubMed

    Yang, Jason H; Saucerman, Jeffrey J

    2012-05-01

    Sympathetic stimulation enhances cardiac contractility by stimulating β-adrenergic signaling and protein kinase A (PKA). Recently, phospholemman (PLM) has emerged as an important PKA substrate capable of regulating cytosolic Ca(2+) transients. However, it remains unclear how PLM contributes to β-adrenergic inotropy. Here we developed a computational model to clarify PLM's role in the β-adrenergic signaling response. Simulating Na(+) and sarcoplasmic reticulum (SR) Ca(2+) clamps, we identify an effect of PLM phosphorylation on SR unloading as the key mechanism by which PLM confers cytosolic Ca(2+) adaptation to long-term β-adrenergic receptor (β-AR) stimulation. Moreover, we show that phospholamban (PLB) opposes and overtakes these actions on SR load, forming a negative feed-forward loop in the β-adrenergic signaling cascade. This network motif dominates the negative feedback conferred by β-AR desensitization and accelerates β-AR-induced inotropy. Model analysis therefore unmasks key actions of PLM phosphorylation during β-adrenergic signaling, indicating that PLM is a critical component of the fight-or-flight response.

  13. Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3T3-L1 preadipocytes.

    PubMed

    Kimura, K; Sasaki, N; Asano, A; Mizukami, J; Kayahashi, S; Kawada, T; Fushiki, T; Morimatsu, M; Yoshida, T; Saito, M

    2000-03-01

    Wild-type or mutated human beta3-adrenergic receptor (Trp64Arg) cDNAs were stably expressed in mouse 3T3-L1 cells. Saturation binding study using a beta-adrenergic ligand revealed that there was no significant difference in the receptor density and the equilibrium dissociation constant between the two cell lines. However, the ability of the mutant beta3-adrenergic receptor to accumulate cyclic AMP (cAMP) in response to isoproterenol was much reduced and Kact for cAMP accumulation was lowered as compared to the wild type receptor. The amount of alpha subunit of stimulatory GTP-binding protein (GSalpha) and adenylyl cyclase activity in response to forskolin were not different in the two cell lines. The responses of the mutant receptor to epinephrine, norepinephrine and L-755,507, a highly specific agonist for human beta3-adrenergic receptor, were also reduced, but the reduction of Kact for L-755,507 was more evident than other agonists tested. The cAMP accumulation in response to some conventional beta3 agonists was less than 10% of that to isoproterenol even in the cells expressing the wild type receptor. These results suggest that the Trp64Arg mutant beta3-adrenergic receptor has less ability to stimulate adenylyl cyclase, and that lipolytic activity through the beta3-adrenergic receptor by catecholamines in subjects carrying this mutation might be suppressed. PMID:10786926

  14. Adrenergic deficiency leads to impaired electrical conduction and increased arrhythmic potential in the embryonic mouse heart.

    PubMed

    Baker, Candice; Taylor, David G; Osuala, Kingsley; Natarajan, Anupama; Molnar, Peter J; Hickman, James; Alam, Sabikha; Moscato, Brittany; Weinshenker, David; Ebert, Steven N

    2012-07-01

    To determine if adrenergic hormones play a critical role in the functional development of the cardiac pacemaking and conduction system, we employed a mouse model where adrenergic hormone production was blocked due to targeted disruption of the dopamine β-hydroxylase (Dbh) gene. Immunofluorescent histochemical evaluation of the major gap junction protein, connexin 43, revealed that its expression was substantially decreased in adrenergic-deficient (Dbh-/-) relative to adrenergic-competent (Dbh+/+ and Dbh+/-) mouse hearts at embryonic day 10.5 (E10.5), whereas pacemaker and structural protein staining appeared similar. To evaluate cardiac electrical conduction in these hearts, we cultured them on microelectrode arrays (8×8, 200 μm apart). Our results show a significant slowing of atrioventricular conduction in adrenergic-deficient hearts compared to controls (31.4±6.4 vs. 15.4±1.7 ms, respectively, p<0.05). To determine if the absence of adrenergic hormones affected heart rate and rhythm, mouse hearts from adrenergic-competent and deficient embryos were cultured ex vivo at E10.5, and heart rates were measured before and after challenge with the β-adrenergic receptor agonist, isoproterenol (0.5 μM). On average, all hearts showed increased heart rate responses following isoproterenol challenge, but a significant (p<0.05) 225% increase in the arrhythmic index (AI) was observed only in adrenergic-deficient hearts. These results show that adrenergic hormones may influence heart development by stimulating connexin 43 expression, facilitating atrioventricular conduction, and helping to maintain cardiac rhythm during a critical phase of embryonic development.

  15. Peripheral nerve response to injury.

    PubMed

    Steed, Martin B

    2011-03-01

    Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

  16. Gustatory Terminal Field Organization and Developmental Plasticity in the Nucleus of the Solitary Tract Revealed through Triple Fluorescent Labeling

    PubMed Central

    May, Olivia L.; Hill, David L.

    2008-01-01

    Early dietary sodium restriction has profound influences on the organization of the gustatory brainstem. However, the anatomical relationships among multiple gustatory nerve inputs have not been examined. Through the use of a triple fluorescence labeling procedure and confocal laser microscopy, terminal fields of the greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves were visualized concurrently in the nucleus of the solitary tract (NTS) of developmentally sodium-restricted and control rats. Dietary sodium restriction during pre- and postnatal development resulted in a two-fold increase in the volume of both the CT and IX nerve terminal fields, but did not affect the volume of the GSP terminal field. In controls, these nerve terminal fields overlapped considerably with each other. The dietary manipulation significantly increased the overlapping zones among terminal fields, resulting in an extension of CT and IX fields past their normal boundaries. The differences in terminal field volumes were exaggerated when expressed relative to the respective NTS volumes. Further, increased terminal field volumes could not be attributed to an increase in the number of afferents because ganglion cell counts did not differ between groups. Taken together, selective increases in terminal field volume and ensuing overlap among terminal fields suggest an increased convergence of these gustatory nerve terminals onto neurons in the NTS. The genesis of such convergence is likely related to disruption of cellular and molecular mechanisms during the development of individual terminal fields, the consequences of which have implications for corresponding functional and behavioral alterations. PMID:16739199

  17. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  18. Optic Nerve Atrophy

    MedlinePlus

    ... with the occipital lobe (the part of the brain that interprets vision) like a cable wire. What is optic nerve ... nystagmus. In older patients, peripheral vision and color vision assessment ... around the brain and spinal cord (hydrocephalus) may prevent further optic ...

  19. RESOLUTION OF THREE DISTINCT POPULATIONS OF NERVE ENDINGS FROM RAT BRAIN HOMOGENATES BY ZONAL ISOPYCNIC CENTRIFUGATION

    PubMed Central

    Bretz, Ursula; Baggiolini, Marco; Hauser, Rolf; Hodel, Christian

    1974-01-01

    Conditions have been established for the fractionation of subcellular components of rat forebrain homogenates by zonal isopycnic equilibration in continuous sucrose density gradients using a B-XIV rotor. The fractions were analyzed biochemically and by ultra-structural morphometry. Starting from postnuclear supernates of forebrain homogenates, it has been possible to resolve three distinct populations of nerve endings from one another, as well as from free mitochondria and myelin fragments. The three types of nerve endings differ in their apparent specific gravity, their biochemical properties, and their ability selectively to accumulate exogenous transmitter substances in vitro. These three particle populations are likely to represent, in order of increasing modal equilibrium density, (a) cholinergic nerve endings, characterized by their high content of acetylcholine, (b) γ-amino butyric acid (GABA)-containing nerve endings with high glutamate decarboxylase activity and the ability to accumulate exogenous GABA, (c) adrenergic nerve endings that accumulate exogenous dopamine and noradrenaline and exhibit high monoamine oxidase activity. PMID:4363959

  20. Fine structure of vesiculated nerve profiles in the human lumbar facet joint.

    PubMed Central

    Vandenabeele, F; Creemers, J; Lambrichts, I; Robberechts, W

    1995-01-01

    The ultrastructural features of vesiculated nerve profiles were examined within a perivascular plexus of unmyelinated nerve fibres around small arteries and arterioles in the posterior facet joint capsule. Such profiles were exclusively observed in the dense fibrous layer and the adjacent part of the subintimal layer. The ligamentum flavum lacked any type of innervation. The vesiculated nerve profiles were tentatively classified on the basis of the fine structural appearances of their vesicular content. Two major types of nerve profiles could readily be distinguished in the capsular tissue. Both displayed a variable number of mitochondria, neurotubules and neurofilaments. The first type, containing predominantly small vesicles with an electron-dense granule or core, was frequently encountered and considered to be adrenergic in function. Profiles similar in morphology were also observed in the synovial plical tissue. A second type of profile, found in the joint capsule, contained varying proportions of small agranular (clear) vesicles and mitochondria. Some of these profiles exhibited an accumulation of mitochondria and were considered to be sensory in function. Nerve profiles filled with predominantly small flattened vesicles were occasionally encountered. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8586567

  1. Optimum Topical Delivery of Adrenergic Agonists to Oral Mucosa Vasculature

    PubMed Central

    Soref, Cheryl M.

    2015-01-01

    Purpose Identify an orotopical vehicle to deliver an α-adrenergic vasoconstrictor to submucosal vasculature that is readily palatable to cancer/bone marrow transplant patients that suppresses chemo-radiotherapy-associated oral mucositis. Methods A [3H] norepinephrine ligand binding assay was developed to quantify receptor binding in hamster oral mucosa. Vehicle components (alcohols, polyols, cellulose, PVP) were tested versus [3H] norepinephrine binding. Vehicle refinement was also done to mask phenylephrine bitter taste and achieve human subject acceptance. The optimized vehicle was tested with α-adrenergic active agents to suppress radiation-induced oral mucositis in mice. Results The ligand binding assay quantified dose- and time-dependent, saturable binding of [3H] norepinephrine. An ethanol:glycerol:propylene glycol:water (6:6:8:80) vehicle provided the best delivery and binding. Further vehicle modification (flavoring and sucralose) yielded a vehicle with excellent taste scores in humans. Addition of phenylephrine, norepinephrine or epinephrine to the optimized vehicle and painting into mouse mouths 20 min before 19 Gy irradiation conferred significant suppression of the weight loss (P < 0.001) observed in mice who received oral vehicle. Conclusion We identified a highly efficient vehicle for the topical delivery of phenylephrine to the oral mucosa of both hamster and human subjects. This will enable its testing to suppress oral mucositis in an upcoming human clinical trial. PMID:25079392

  2. Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy

    SciTech Connect

    Mechler, F.; Mastaglia, F.L.

    1981-02-01

    The pharmacological responses of vascular adrenergic receptors to intravenously administered epinephrine, phentolamine, and propranolol were assessed by measuring muscle blood flow (MBF) changes in the tibialis anterior muscle using the xenon 133 clearance technique and were compared in 8 normal subjects and 11 patients with myotonic dystrophy. In cases with advanced involvement of the muscle, the resting MBF was reduced and was not significantly altered by epinephrine before or after alpha- or beta-receptor blockade. In patients in whom the tibialis anterior muscle was normal or only minimally affected clinically, a paradoxical reduction in the epinephrine-induced increase in MBF was found after alpha blockade by phentolamine, and the epinephrine-induced MBF increase was not completely blocked by propranolol as in the normal subjects. These findings point to functional alteration in the properties of vascular adrenergic receptors in muscle in myotonic dystrophy. While this may be another manifestation of a widespread cell membrane defect in the disease, the possibility that the changes are secondary to the myotonic state cannot be excluded.

  3. The Principles of Ligand Specificity on beta-2-adrenergic receptor

    PubMed Central

    Chan, H. C. Stephen; Filipek, Slawomir; Yuan, Shuguang

    2016-01-01

    G protein-coupled receptors are recognized as one of the largest families of membrane proteins. Despite sharing a characteristic seven-transmembrane topology, G protein-coupled receptors regulate a wide range of cellular signaling pathways in response to various physical and chemical stimuli, and prevail as an important target for drug discovery. Notably, the recent progress in crystallographic methods led to a breakthrough in elucidating the structures of membrane proteins. The structures of β2-adrenergic receptor bound with a variety of ligands provide atomic details of the binding modes of agonists, antagonists and inverse agonists. In this study, we selected four representative molecules from each functional class of ligands and investigated their impacts on β2-adrenergic receptor through a total of 12 × 100 ns molecular dynamics simulations. From the obtained trajectories, we generated molecular fingerprints exemplifying propensities of protein-ligand interactions. For each functional class of compounds, we characterized and compared the fluctuation of the protein backbone, the volumes in the intracellular pockets, the water densities in the receptors, the domain interaction networks as well as the movements of transmembrane helices. We discovered that each class of ligands exhibits a distinct mode of interactions with mainly TM5 and TM6, altering the shape and eventually the state of the receptor. Our findings provide insightful prospective into GPCR targeted structure-based drug discoveries. PMID:27703221

  4. Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management.

    PubMed

    Ortega, V E

    2014-07-01

    Beta2 (β2) adrenergic receptor agonists (beta agonists) are a commonly prescribed treatment for asthma despite the small increase in risk for life-threatening adverse responses associated with long-acting beta agonist (LABA). The concern for life-threatening adverse effects associated with LABA and the inter-individual variability of therapeutic responsiveness to LABA-containing combination therapies provide the rationale for pharmacogenetic studies of beta agonists. These studies primarily evaluated genes within the β2-adrenergic receptor and related pathways; however, recent genome-wide studies have identified novel loci for beta agonist response. Recent studies have identified a role for rare genetic variants in determining beta agonist response and, potentially, the risk for rare, adverse responses to LABA. Before genomics research can be applied to the development of genetic profiles for personalized medicine, it will be necessary to continue adapting to the analysis of an increasing volume of genetic data in larger cohorts with a combination of analytical methods and in vitro studies.

  5. Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin

    SciTech Connect

    Shepherd, R.E.; Lang, C.H.; McDonough, K.H.

    1987-02-01

    A dose-dependent impairment of intrinsic myocardial performance has been observed following in vivo administration of endotoxin. The present study reports a dose-dependent increase in plasma catecholamines following endotoxin (ET) that may impair ..beta..-adrenergic responsiveness. Hearts were removed from pentobarbital-anesthetized rats 4 h after a bolus injection of saline or ET and were studied as isolated cell preparations following collagenase digestion. Responsiveness of isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in myocytes prepared from hearts of animals injected with 10 and 100 ..mu..g ET was decreased when compared with control rats and was significantly blunted in myocytes prepared from animals receiving 1000 ..mu..g ET. Similar sensitivities of the cAMP system existed, as judged by similar half-maximum effective concentration values. cAMP accumulation in the presence of 1 ..mu..M forskolin was depressed in myocytes from the 1000-..mu..g ET animals; ..beta..-adrenergic receptor density was decreased 25% in myocytes from high-dose ET animals when compared with control animals. This was accompanied by a nonsignificant reduction in the affinity of binding sites for (+/-)(/sup 3/H)CGP 12177. The blunted myocyte hormonal responsiveness following ET challenge appears to be related to the decreased activity of the adenylate cyclase that may be attributed to alterations in both receptor density and in the adenylate cyclase itself.

  6. The role of α-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man.

    PubMed

    Fairfax, Seth T; Holwerda, Seth W; Credeur, Daniel P; Zuidema, Mozow Y; Medley, John H; Dyke, Peter C; Wray, D Walter; Davis, Michael J; Fadel, Paul J

    2013-07-15

    Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P = 0.016) and then robustly decreased to a nadir of -5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1 ± 0.7% and -0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors.

  7. AB257. The study of the influence of the changes in alpha 1-adrenergic receptor and NGF on the diabetic urethral function

    PubMed Central

    Chen, Shouzhen; Wang, Wenfu; Zhu, Kejia; Zhang, Dongqing; Wang, Yong; Shi, Benkang

    2016-01-01

    Background To study the influence of the changes in the α1-adrenergic receptor and NGF/ProNGF pathway on the diabetic urethral function. Methods A total of 20 female Wistar rats were divided into two groups equally at random. Urethral function was examined by recordings of bladder pressure and urethral perfusion pressure (UPP). The expression of α1-adrenergic receptor in the urethra was measured via RT-qPCR and ELISA method. The expression of nerve growth factor (NGF) in the urethra was measured via RT-qPCR and ELISA method. The expression of proNGF, P75NTR and sortilin in the urethra was measured by western blotting. Results The lowest urethral pressure (UPP nadir) during urethral relaxation was higher in diabetic rats. The UPP nadir and baseline UPP in diabetic rats was significantly decreased by intravenous administration of the α1-adrenoceptor antagonist (tamsulosin). The α1a and α1d adrenergic receptor in the urethra of the diabetic group was significantly increased via RT-qPCR and western blotting (P<0.05). The RT-qPCR and ELISA studies showed a significant decrease of NGF and the western blotting studies showed a significant increase of proNGF (P<0.05). There was a statistical decrease of the P75NTR in the urethras of diabetic rats (P<0.05) and no significant difference concerning sortilin between two groups (P>0.05). Conclusions The increase in the expression of α1-adrenoceptor and changes of the NGF/ProNGF pathway in the diabetic urethral was a possible mechanism of the diabetic urethral dysfunction.

  8. Variation in Lingual Nerve Course: A Human Cadaveric Study

    PubMed Central

    Al-Amery, Samah M.; Nambiar, Phrabhakaran; Naidu, Murali

    2016-01-01

    The lingual nerve is a terminal branch of the mandibular nerve. It is varied in its course and in its relationship to the mandibular alveolar crest, submandibular duct and also the related muscles in the floor of the mouth. This study aims to understand the course of the lingual nerve from the molar area until its insertion into the tongue muscle. This cadaveric research involved the study of 14 hemi-mandibles and consisted of two parts: (i) obtaining morphometrical measurements of the lingual nerve to three landmarks on the alveolar ridge, and (b) understanding non-metrical or morphological appearance of its terminal branches inserting in the ventral surface of the tongue. The mean distance between the fourteen lingual nerves and the alveolar ridge was 12.36 mm, and they were located 12.03 mm from the lower border of the mandible. These distances were varied when near the first molar (M1), second molar (M2) and third molar (M3). The lingual nerve coursed on the floor of the mouth for approximately 25.43 mm before it deviated toward the tongue anywhere between the mesial of M1 and distal of M2. Thirteen lingual nerves were found to loop around the submandibular duct for an average distance of 6.92 mm (95% CI: 5.24 to 8.60 mm). Their looping occurred anywhere between the M2 and M3. In 76.9% of the cases the loop started around the M3 region and the majority (69.2%) of these looping ended at between the first and second molars and at the lingual developmental groove of the second molar. It gave out as many as 4 branches at its terminal end at the ventral surface of the tongue, with the presence of 2 branches being the most common pattern. An awareness of the variations of the lingual nerve is important to prevent any untoward complications or nerve injury and it is hoped that these findings will be useful for planning of surgical procedures related to the alveolar crest, submandibular gland/ duct and surrounding areas. PMID:27662622

  9. Selective α1-adrenergic blockade disturbs the regional distribution of cerebral blood flow during static handgrip exercise.

    PubMed

    Fernandes, Igor A; Mattos, João D; Campos, Monique O; Machado, Alessandro C; Rocha, Marcos P; Rocha, Natalia G; Vianna, Lauro C; Nobrega, Antonio C L

    2016-06-01

    Handgrip-induced increases in blood flow through the contralateral artery that supplies the cortical representation of the arm have been hypothesized as a consequence of neurovascular coupling and a resultant metabolic attenuation of sympathetic cerebral vasoconstriction. In contrast, sympathetic restraint, in theory, inhibits changes in perfusion of the cerebral ipsilateral blood vessels. To confirm whether sympathetic nerve activity modulates cerebral blood flow distribution during static handgrip (SHG) exercise, beat-to-beat contra- and ipsilateral internal carotid artery blood flow (ICA; Doppler) and mean arterial pressure (MAP; Finometer) were simultaneously assessed in nine healthy men (27 ± 5 yr), both at rest and during a 2-min SHG bout (30% maximal voluntary contraction), under two experimental conditions: 1) control and 2) α1-adrenergic receptor blockade. End-tidal carbon dioxide (rebreathing system) was clamped throughout the study. SHG induced increases in MAP (+31.4 ± 10.7 mmHg, P < 0.05) and contralateral ICA blood flow (+80.9 ± 62.5 ml/min, P < 0.05), while no changes were observed in the ipsilateral vessel (-9.8 ± 39.3 ml/min, P > 0.05). The reduction in ipsilateral ICA vascular conductance (VC) was greater compared with contralateral ICA (contralateral: -0.8 ± 0.8 vs. ipsilateral: -2.6 ± 1.3 ml·min(-1)·mmHg(-1), P < 0.05). Prazosin was effective to induce α1-blockade since phenylephrine-induced increases in MAP were greatly reduced (P < 0.05). Under α1-adrenergic receptor blockade, SHG evoked smaller MAP responses (+19.4 ± 9.2, P < 0.05) but similar increases in ICAs blood flow (contralateral: +58.4 ± 21.5 vs. ipsilateral: +54.3 ± 46.2 ml/min, P > 0.05) and decreases in VC (contralateral: -0.4 ± 0.7 vs. ipsilateral: -0.4 ± 1.0 ml·min(-1)·mmHg(-1), P > 0.05). These findings indicate a role of sympathetic nerve activity in the regulation of cerebral blood flow distribution during SHG.

  10. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

    PubMed Central

    Canning, Brendan J.; Merlo-Pich, Emilio; Woodcock, Ashley A.; Smith, Jaclyn A.

    2015-01-01

    Rationale: Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Objectives: Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. Methods: A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. Measurements and Main Results: We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. Conclusions: PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle–associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting. PMID:25906337

  11. Thermogenic responsiveness to nonspecific beta-adrenergic stimulation is not related to genetic variation in codon 16 of the beta2-adrenergic receptor.

    PubMed

    Bell, Christopher; Stob, Nicole R; Seals, Douglas R

    2006-04-01

    Stimulation of beta-adrenergic receptors (beta-AR) by the sympathetic nervous system (SNS) modulates energy expenditure (EE), but substantial interindividual variability is observed. We determined whether the thermogenic response to beta-AR stimulation is related to genetic variation in codon 16 of the beta(2)-AR, a biologically important beta-AR polymorphism, and whether differences in SNS activity (i.e., the stimulus for agonist-promoted downregulation) are involved. The increase in EE (DeltaEE, indirect calorimetry, ventilated hood) above resting EE in response to nonspecific beta-AR stimulation [iv isoproterenol: 6, 12, and 24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans [Arg16Arg: 9 male, 7 female, 48 +/- 5 yr; Arg16Gly: 11 male, 4 female, 53 +/- 5 yr; Gly16Gly: 3 male, 12 female, 48 +/- 5 yr (means +/- SE)]. Neither FFM-adjusted baseline resting EE (P = 0.83) nor the dose of isoproterenol required to increase EE 10% above resting (P = 0.87) differed among the three groups (Arg16Arg: 5,409 +/- 209 kJ/day, 11.2 +/- 2.1 ng x kg FFM(-1) x min(-1); Arg16Gly: 5,367 +/- 272 kJ/day, 11.1 +/- 2.1 ng x kg FFM(-1) x min(-1); Gly16Gly: 5,305 +/- 159 kJ/day, 10.5 +/- 1.4 ng x kg FFM(-1) x min(-1)). Consistent with this, muscle sympathetic nerve activity and plasma norepinephrine concentrations were not different among the groups. Group differences in sex composition did not influence the results. Our findings indicate that the thermogenic response to nonspecific beta-AR stimulation, an important mechanistic component of overall beta-AR modulation of EE, is not related to this beta(2)-AR polymorphism in healthy humans. This may be explained in part by a lack of association between this gene variant and tonic SNS activity.

  12. Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans.

    PubMed

    Pueyo, Esther; Orini, Michele; Rodríguez, José F; Taggart, Peter

    2016-08-01

    Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and β-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (β-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4minutes of phasic β-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic β-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic β-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events. PMID:27178727

  13. T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure.

    PubMed

    Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Yan, Ping; Loew, Leslie M; Poggesi, Corrado; Cerbai, Elisabetta; Pavone, Francesco S; Sacconi, Leonardo

    2016-01-01

    Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca(2+) release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca(2+) transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca(2+) sparks, reduces Ca(2+) transient variability, and hastens the decay of Ca(2+) transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca(2+) rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca(2+) rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity. PMID:27598150

  14. Purification and reconstitution of the human platelet. cap alpha. /sub 2/-adrenergic receptor

    SciTech Connect

    Regan, J.W.; Cerione, R.A.; Nakata, H.; Benovic, J.L.; DeMarinis, R.M.; Caron, M.G.; Lefkowitz, R.J.

    1986-05-01

    Human platelet ..cap alpha../sub 2/-adrenergic receptors have been purified approx.80,000 fold to apparent homogeneity by a five step chromatographic procedure. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radioiodinated protein from purified receptor preparations shows a single major band of M/sub r/ 64,000. The competitive binding of ligands to the purified receptor protein shows the proper ..cap alpha../sub 2/-adrenergic specificity. The ..cap alpha../sub 2/-adrenergic receptor contains an essential sulfhydryl residues. Thus, exposure of the purified receptor to the sulfhydryl specific reagent, phenylmercuric chloride (PMC), resulted in a 80% loss of binding activity. This loss of binding activity was prevented when exposure to PMC was done in the presence of ..cap alpha../sub 2/-adrenergic ligands and it was reversed by subsequent exposure to dithiothreitol. Partial proteolysis of purified ..cap alpha../sub 2/-adrenergic receptors was obtained with S. aureus V-8 protease, ..cap alpha..-chymotrypsin and papain. In a comparison with purified ..beta../sub 2/-adrenergic receptors no common partial proteolytic products were found. Partially purified preparations of the ..cap alpha../sub 2/-adrenergic receptor were successfully reconstituted into phospholipid vesicles with the inhibitory guanyl nucleotide-binding regulatory protein, N/sub i/. In these reconstituted preparations, epinephrine could stimulate, and phentolamine could block, the GTPase activity of N/sub i/.

  15. T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure

    PubMed Central

    Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Yan, Ping; Loew, Leslie M.; Poggesi, Corrado; Cerbai, Elisabetta; Pavone, Francesco S.; Sacconi, Leonardo

    2016-01-01

    Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca2+ release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca2+ transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca2+ sparks, reduces Ca2+ transient variability, and hastens the decay of Ca2+ transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca2+ rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca2+ rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity. PMID:27598150

  16. β-adrenergic receptor responsiveness in aging heart and clinical implications

    PubMed Central

    Ferrara, Nicola; Komici, Klara; Corbi, Graziamaria; Pagano, Gennaro; Furgi, Giuseppe; Rengo, Carlo; Femminella, Grazia D.; Leosco, Dario; Bonaduce, Domenico

    2014-01-01

    Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called “β-adrenergic desensitization”). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure. PMID:24409150

  17. Progesterone prevents linkage of rabbit myometrial alpha 2-adrenergic receptors to inhibition of adenylate cyclase.

    PubMed

    Wu, Y Y; Riemer, R K; Goldfien, A; Roberts, J M

    1989-04-01

    The uterine response to adrenergic stimulation is determined by the hormonal milieu. This response is particularly well characterized in the rabbit. In this species, as in humans, the response of the uterus to sympathetic stimulation is alpha-adrenergically mediated contraction with elevated circulating estrogen. However, with progesterone predominance, similar stimulation inhibits uterine contractions, a response mediated by beta-adrenergic receptors acting through their second message, cyclic adenosine monophosphate. We studied the mechanisms by which sex steroids regulate myometrial adrenergic responses. In this study, we questioned whether part of the effect of sex steroids could be explained by an alteration of the coupling of the alpha 2-adrenergic receptor to the inhibition of adenylate cyclase. We found that in the progesterone-treated rabbit, although alpha 2-receptors are present, they are not linked to inhibition of cyclic adenosine monophosphate synthesis. The net synthesis of cyclic adenosine monophosphage in response to endogenous catecholamines is determined by their activation of beta-adrenergic receptors to increase and alpha 2-receptors to decrease cyclic adenosine monophosphate formation. Thus the uncoupling of alpha 2-receptors contributes to increased intracellular cyclic adenosine monophosphate in myometrium of progesterone-treated animals consistent with the reported predominance of beta-adrenergic contractile responses in this setting.

  18. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

    PubMed Central

    Vyas, Alka A.; Patel, Himatkumar V.; Fromholt, Susan E.; Heffer-Lauc, Marija; Vyas, Kavita A.; Dang, Jiyoung; Schachner, Melitta; Schnaar, Ronald L.

    2002-01-01

    Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering. PMID:12060784

  19. Ultrasound of Peripheral Nerves

    PubMed Central

    Suk, Jung Im; Walker, Francis O.; Cartwright, Michael S.

    2013-01-01

    Over the last decade, neuromuscular ultrasound has emerged as a useful tool for the diagnosis of peripheral nerve disorders. This article reviews sonographic findings of normal nerves including key quantitative ultrasound measurements that are helpful in the evaluation of focal and possibly generalized peripheral neuropathies. It also discusses several recent papers outlining the evidence base for the use of this technology, as well as new findings in compressive, traumatic, and generalized neuropathies. Ultrasound is well suited for use in electrodiagnostic laboratories where physicians, experienced in both the clinical evaluation of patients and the application of hands-on technology, can integrate findings from the patient’s history, physical examination, electrophysiological studies, and imaging for diagnosis and management. PMID:23314937

  20. Cranial Nerve II: Vision.

    PubMed

    Gillig, Paulette Marie; Sanders, Richard D

    2009-09-01

    This article contains a brief review of the anatomy of the visual system, a survey of diseases of the retina, optic nerve and lesions of the optic chiasm, and other visual field defects of special interest to the psychiatrist. It also includes a presentation of the corticothalamic mechanisms, differential diagnosis, and various manifestations of visual illusions, and simple and complex visual hallucinations, as well as the differential diagnoses of these various visual phenomena. PMID:19855858

  1. [Suprascapular nerve entrapment].

    PubMed

    Fansa, H; Schneider, W

    2003-03-01

    Isolated compression of the suprascapular nerve is a rare entity, that is seldom considered in differential diagnosis of shoulder pain. Usually atrophy of supraspinatus and infraspinatus muscles is present, resulting in weakened abduction and external rotation of the shoulder. Mostly the patients do not note the paresis, but complain about a dull and burning pain over the dorsal shoulder region. In a proximal lesion (at level of the superior transverse scapular ligament) electromyography reveals changes in both muscles, while in a distal lesion (spinoglenoidal notch) only the infraspinatus shows a pathology. From 1996 to 2001 we diagnosed an isolated suprascapular entrapment in nine patients. Seven patients were operated: The ligament was removed and the nerve was neurolysed. The average age was 36 years. All patients showed pathological findings in electrophysiological and clinical examination. Five patients had an atrophy of both scapula muscles, two showed only infraspinatus muscle atrophy (one with a ganglion in the distal course of the nerve). Six patients were followed up. All showed an improvement. Pain disappeared and all patients were able to return to work and sport activities. Electrophysiological examination one year after operation revealed normal nerve conduction velocity. The number of motor units, however, showed a reduction by half compared to the healthy side. Lesions without history of trauma are usually caused by repetitive motion or posture. Weight lifting, volley ball and tennis promote the entrapment. Rarely a lesion (either idiopathic or due to external compression) is described for patients who underwent surgery. Patients with a ganglion or a defined cause of compression should be operated, patients who present without a distinct reason for compression should firstly be treated conservatively. Physiotherapy, antiphlogistic medication and avoiding of the pain triggering motion can improve the symptoms. However, if muscle atrophy is evident

  2. Peripheral nerve hyperexcitability syndromes.

    PubMed

    Küçükali, Cem Ismail; Kürtüncü, Murat; Akçay, Halil İbrahim; Tüzün, Erdem; Öge, Ali Emre

    2015-01-01

    Peripheral nerve hyperexcitability (PNH) syndromes can be subclassified as primary and secondary. The main primary PNH syndromes are neuromyotonia, cramp-fasciculation syndrome (CFS), and Morvan's syndrome, which cause widespread symptoms and signs without the association of an evident peripheral nerve disease. Their major symptoms are muscle twitching and stiffness, which differ only in severity between neuromyotonia and CFS. Cramps, pseudomyotonia, hyperhidrosis, and some other autonomic abnormalities, as well as mild positive sensory phenomena, can be seen in several patients. Symptoms reflecting the involvement of the central nervous system occur in Morvan's syndrome. Secondary PNH syndromes are generally seen in patients with focal or diffuse diseases affecting the peripheral nervous system. The PNH-related symptoms and signs are generally found incidentally during clinical or electrodiagnostic examinations. The electrophysiological findings that are very useful in the diagnosis of PNH are myokymic and neuromyotonic discharges in needle electromyography along with some additional indicators of increased nerve fiber excitability. Based on clinicopathological and etiological associations, PNH syndromes can also be classified as immune mediated, genetic, and those caused by other miscellaneous factors. There has been an increasing awareness on the role of voltage-gated potassium channel complex autoimmunity in primary PNH pathogenesis. Then again, a long list of toxic compounds and genetic factors has also been implicated in development of PNH. The management of primary PNH syndromes comprises symptomatic treatment with anticonvulsant drugs, immune modulation if necessary, and treatment of possible associated dysimmune and/or malignant conditions. PMID:25719304

  3. Optic nerve hypoplasia

    PubMed Central

    Kaur, Savleen; Jain, Sparshi; Sodhi, Harsimrat B. S.; Rastogi, Anju; Kamlesh

    2013-01-01

    Optic nerve hypoplasia (ONH) is a congenital anomaly of the optic disc that might result in moderate to severe vision loss in children. With a vast number of cases now being reported, the rarity of ONH is obviously now refuted. The major aspects of ophthalmic evaluation of an infant with possible ONH are visual assessment, fundus examination, and visual electrophysiology. Characteristically, the disc is small, there is a peripapillary double-ring sign, vascular tortuosity, and thinning of the nerve fiber layer. A patient with ONH should be assessed for presence of neurologic, radiologic, and endocrine associations. There may be maternal associations like premature births, fetal alcohol syndrome, maternal diabetes. Systemic associations in the child include endocrine abnormalities, developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus callosum abnormalities. There is a greater incidence of clinical neurologic abnormalities in patients with bilateral ONH (65%) than patients with unilateral ONH. We present a review on the available literature on the same to urge caution in our clinical practice when dealing with patients with ONH. Fundus photography, ocular coherence tomography, visual field testing, color vision evaluation, neuroimaging, endocrinology consultation with or without genetic testing are helpful in the diagnosis and management of ONH. (Method of search: MEDLINE, PUBMED). PMID:24082663

  4. Impaired chronotropic response to exercise in mice lacking catecholamines in adrenergic cells.

    PubMed

    Bao, Xuping; Liu, Fujun; Gu, Yusu; Lu, Chuanyi M; Ziegler, Michael G

    2008-12-01

    To define the in vivo role of adrenergic catecholamines (CAs), we generated a mouse model whereby tyrosine hydroxylase (TH) was knocked out (KO) in phenylethanolamine N-methyltransferase-expressing cells. These adrenergic specific TH-KO mice were viable and grossly normal. Their resting heart rate and blood pressure, as monitored by telemetry, were unchanged. However, when challenged with treadmill exercise, their chronotropic responses were significantly reduced by 14% compared to wild-type mice. Thus, our data suggest that adrenergic CA is required for normal chronotropic responses to stress, but not required for prenatal and postnatal development or normal cardiovascular function at rest.

  5. Alpha-1-adrenergic receptors: targets for agonist drugs to treat heart failure.

    PubMed

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

    2011-10-01

    Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down-regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart might represent a novel and effective way to treat heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

  6. Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol.

    PubMed

    Kern, Christopher; Meyer, Thorsten; Droux, Serge; Schollmeyer, Dieter; Miculka, Christian

    2009-03-26

    The beta-adrenergic agonist 1 (zilpaterol) is used as production enhancer in cattle. Binding experiments of separated enantiomers on recombinant human beta(2)-adrenergic and mu-opioid receptors and functional studies showed that the (-)-1 enantiomer accounts for essentially all the beta(2)-adrenergic agonist activity and that it exhibits less affinity toward the mu-opioid receptor than (+)-1, which is a mu-opioid receptor antagonist. X-ray crystallography revealed the absolute configuration of (-)-1 to be 6R,7R.

  7. β1-adrenergic receptor antagonists signal via PDE4 translocation.

    PubMed

    Richter, Wito; Mika, Delphine; Blanchard, Elise; Day, Peter; Conti, Marco

    2013-03-01

    It is generally assumed that antagonists of Gs-coupled receptors do not activate cAMP signalling, because they do not stimulate cAMP production via Gs-protein/adenylyl cyclase activation. Here, we report a new signalling pathway whereby antagonists of β1-adrenergic receptors (β1ARs) increase cAMP levels locally without stimulating cAMP production directly. Binding of antagonists causes dissociation of a preformed complex between β1ARs and Type-4 cyclic nucleotide phosphodiesterases (PDE4s). This reduces the local concentration of cAMP-hydrolytic activity, thereby increasing submembrane cAMP and PKA activity. Our study identifies receptor/PDE4 complex dissociation as a novel mechanism of antagonist action that contributes to the pharmacological properties of β1AR antagonists and might be shared by other receptor subtypes.

  8. Agonist-Directed Desensitization of the β2-Adrenergic Receptor

    PubMed Central

    Goral, Vasiliy; Jin, Yan; Sun, Haiyan; Ferrie, Ann M.; Wu, Qi; Fang, Ye

    2011-01-01

    The β2-adrenergic receptor (β2AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β2AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β2AR desensitization at the whole cell level. PMID:21541288

  9. Optimization of a wearable pudendal nerve stimulator using computational models.

    PubMed

    Shiraz, Arsam N; Leaker, Brian; Demosthenous, Andreas

    2015-01-01

    After spinal cord injury, lower urinary tract functions may be disrupted. Trans-rectal stimulation of the pudendal nerve may enable patients to regain these functions via minimally invasive means. Using a finite element model of a wearable trans-rectal stimulator in the pelvic region, and a computational model of mammalian nerve fiber, various electrode configurations and the corresponding required current levels were studied. A configuration requiring considerably lower current level than previously reported was identified. For this configuration, the strength-duration curve was simulated and the effect of different stimulus waveforms on the required current was studied. In addition, the study examined whether a multi-electrode device could selectively activate different terminal branches of the pudendal nerve.

  10. Optimization of a wearable pudendal nerve stimulator using computational models.

    PubMed

    Shiraz, Arsam N; Leaker, Brian; Demosthenous, Andreas

    2015-01-01

    After spinal cord injury, lower urinary tract functions may be disrupted. Trans-rectal stimulation of the pudendal nerve may enable patients to regain these functions via minimally invasive means. Using a finite element model of a wearable trans-rectal stimulator in the pelvic region, and a computational model of mammalian nerve fiber, various electrode configurations and the corresponding required current levels were studied. A configuration requiring considerably lower current level than previously reported was identified. For this configuration, the strength-duration curve was simulated and the effect of different stimulus waveforms on the required current was studied. In addition, the study examined whether a multi-electrode device could selectively activate different terminal branches of the pudendal nerve. PMID:26737021

  11. Constitutive glycogen synthase kinase-3α/β activity protects against chronic β-adrenergic remodelling of the heart

    PubMed Central

    Webb, Ian G.; Nishino, Yasuhiro; Clark, James E.; Murdoch, Colin; Walker, Simon J.; Makowski, Marcus R.; Botnar, Rene M.; Redwood, Simon R.; Shah, Ajay M.; Marber, Michael S.

    2010-01-01

    Aims Glycogen synthase kinase 3 (GSK-3) signalling is implicated in the growth of the heart during development and in response to stress. However, its precise role remains unclear. We set out to characterize developmental growth and response to chronic isoproterenol (ISO) stress in knockin (KI) mice lacking the critical N-terminal serines, 21 of GSK-3α and 9 of GSK-3β respectively, required for inactivation by upstream kinases. Methods and results Between 5 and 15 weeks, KI mice grew more rapidly, but normalized heart weight and contractile performance were similar to wild-type (WT) mice. Isolated hearts of both genotypes responded comparably to acute ISO infusion with increases in heart rate and contractility. In WT mice, chronic subcutaneous ISO infusion over 14 days resulted in cardiac hypertrophy, interstitial fibrosis, and impaired contractility, accompanied by foetal gene reactivation. These effects were all significantly attenuated in KI mice. Indeed, ISO-treated KI hearts demonstrated reversible physiological remodelling traits with increased stroke volume and a preserved contractile response to acute adrenergic stimulation. Furthermore, simultaneous pharmacological inhibition of GSK-3 in KI mice treated with chronic subcutaneous ISO recapitulated the adverse remodelling phenotype seen in WT hearts. Conclusion Expression of inactivation-resistant GSK-3α/β does not affect eutrophic myocardial growth but protects against pathological hypertrophy induced by chronic adrenergic stimulation, maintaining cardiac function and attenuating interstitial fibrosis. Accordingly, strategies to prevent phosphorylation of Ser-21/9, and consequent inactivation of GSK-3α/β, may enable a sustained cardiac response to chronic β-agonist stimulation while preventing pathological remodelling. PMID:20299330

  12. [Electrical nerve stimulation for plexus and nerve blocks].

    PubMed

    Birnbaum, J; Klotz, E; Bogusch, G; Volk, T

    2007-11-01

    Despite the increasing use of ultrasound, electrical nerve stimulation is commonly used as the standard for both plexus and peripheral nerve blocks. Several recent randomized trials have contributed to a better understanding of physiological and clinical correlations. Traditionally used currents and impulse widths are better defined in relation to the distance between needle tip and nerves. Commercially available devices enable transcutaneous nerve stimulation and provide new opportunities for the detection of puncture sites and for training. The electrically ideal position of the needle usually is defined by motor responses which can not be interpreted without profound anatomical knowledge. For instance, interscalene blocks can be successful even after motor responses of deltoid or pectoral muscles. Infraclavicular blocks should be aimed at stimulation of the posterior fascicle (extension). In contrast to multiple single nerve blocks, axillary single-shot blocks more commonly result in incomplete anaesthesia. Blockade of the femoral nerve can be performed without any nerve stimulation if the fascia iliaca block is used. Independently of the various approaches to the sciatic nerve, inversion and plantar flexion are the best options for single-shot blocks. Further clinical trials are needed to define the advantages of stimulating catheters in continuous nerve blocks.

  13. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    PubMed Central

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  14. Age-dependent changes in expression of alpha/sub 1/-adrenergic receptors in rat myocardium

    SciTech Connect

    Schaffer, W.; Williams, R.S.

    1986-07-16

    The expression of alpha/sub 1/-adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from (/sup 125/I) 2-(..beta.. hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha/sub 1/-adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha/sub 1/-adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha/sub 1/-adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium.

  15. Alpha 2 adrenergic receptors in hyperplastic human prostate: identification and characterization using (/sup 3/H) rauwolscine

    SciTech Connect

    Shapiro, E.; Lepor, H.

    1986-05-01

    (/sup 3/H)Rauwolscine ((/sup 3/H)Ra), a selective ligand for the alpha 2 adrenergic receptor, was used to identify and characterize alpha 2 adrenergic receptors in prostate glands of men with benign prostatic hyperplasia. Specific binding of (/sup 3/H)Ra to prostatic tissue homogenates was rapid and readily reversible by addition of excess unlabelled phentolamine. Scatchard analysis of saturation experiments demonstrates a single, saturable class of high affinity binding sites (Bmax = 0.31 +/- 0.04 fmol./microgram. DNA, Kd = 0.9 +/- 0.11 nM.). The relative potency of alpha adrenergic drugs (clonidine, alpha-methylnorepinephrine and prazosin) in competing for (/sup 3/H)Ra binding sites was consistent with the order predicted for an alpha 2 subtype. The role of alpha 2 adrenergic receptors in normal prostatic function and in men with bladder outlet obstruction secondary to BPH requires further investigation.

  16. Dissociation between renin and arterial pressure responses to beta-adrenergic blockade in human essential hypertension.

    PubMed

    Bravo, E L; Tarazi, R C; Dustan, H P; Lewis, J W

    1975-06-01

    Studies were carried out in 69 patients with essential hypertension to examine the relationship between changes in plasma renin activity (PRA) and arterial pressure (BP) in response to a beta-adrenergic blocking agent, propranolol. PRA had no consistent relationship with BP during treatment, either in patients receiving propranolol alone (r = 0.12) or in those receiving a combination of diuretics and propranolol (r = 0.18). Furthermore, long-term beta-adrenergic blockade failed to inhibit increases of PRA induced by diuretics or rapid sodium depletion. These results indicate that (1) beta-adrenergic blockade can reduce BP by mechanisms other than PRA suppression; and (2) the beta-adrenergic nervous system is important, but not essential, for renin release. PMID:236841

  17. Dihydrotestosterone decreases beta-adrenergic receptor binding in the fetal rabbit lung.

    PubMed

    Moawad, A H; River, L P; River, J M

    1988-07-01

    Tritium-labeled dihydroalprenolol was used to quantify the beta-adrenergic receptor sites in day 30 fetal rabbit lung tissue. Each of the fetuses of New Zealand White rabbits on day 28 of gestation was injected with dihydrotestosterone (2.0 micrograms) in one horn of the uterus and 10% ethanol in normal saline (the solvent) in the contralateral one. The animals were sacrificed 48 hours later and the fetal lung tissue was assayed. Dihydrotestosterone decreased the beta-adrenergic receptor site number in the treatment group compared with the control group (86 versus 111 fmol/mg protein, p less than 0.05 by paired t-test). In the presence of dihydrotestosterone, beta-adrenergic receptor binding is inhibited in the preterm fetal rabbit. This effect may be implicated in the beta-adrenergic mediation of phospholipid synthesis and/or release by fetal alveolar cells.

  18. Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats

    PubMed Central

    Khimsuksri, Sawita; Wyss, J. Michael; Thaeomor, Atcharaporn; Paphangkorakit, Jarin; Jirakulsomchok, Dusit; Roysommuti, Sanya

    2016-01-01

    Perinatal taurine excess or deficit influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed normal rat chow with 3% β-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Their male offspring were fed normal rat chow and tap water throughout the experiment. At 8–10 weeks of age, blood chemistry, arterial pressure, heart rate and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low (0.3–0.5 Hz) and high frequency (0.5–4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups, while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve and arterial pressure power spectral densities in the 0.3–4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very low frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in

  19. A Cadaveric Study of the Communication Patterns Between the Buccal Trunks of the Facial Nerve and the Infraorbital Nerve in the Midface.

    PubMed

    Tansatit, Tanvaa; Phanchart, Piyaporn; Chinnawong, Dawinee; Apinuntrum, Prawit; Phetudom, Thavorn; Sahraoui, Yasmina M E

    2016-01-01

    Most nerve communications reported in the literature were found between the terminal branches. This study aimed to clarify and classify patterns of proximal communications between the buccal branches (BN) of the facial nerve and the infraorbital nerve (ION).The superficial musculoaponeurotic system protects any communication sites from conventional dissections. Based on this limitation, the soft tissues of each face were peeled off the facial skull and the facial turn-down flap specimens were dissected from the periosteal view. Dissection was performed in 40 hemifaces to classify the communications in the sublevator space. Communication site was measured from the ala of nose.A double communication was the most common type found in 62.5% of hemifaces. Triple and single communications existed in 25% and 10% of 40 hemiface specimens, respectively. One hemiface had no communication. The most common type of communication occurred between the lower trunk of the BN of the facial nerve and the lateral labial (fourth) branch of the ION (70% in 40 hemifaces). Communication site was deep to the levator labii superioris muscle at 16.2 mm from the nasal ala. Communications between the motor and the sensory nerves in the midface may be important to increase nerve endurance and to compensate functional loss from injury.Proximal communications between the main trunks of the facial nerve and the ION in the midface exist in every face. This implies some specific functions in normal individuals. Awareness of these nerves is essential in surgical procedure in the midface.

  20. [Imaging anatomy of cranial nerves].

    PubMed

    Hermier, M; Leal, P R L; Salaris, S F; Froment, J-C; Sindou, M

    2009-04-01

    Knowledge of the anatomy of the cranial nerves is mandatory for optimal radiological exploration and interpretation of the images in normal and pathological conditions. CT is the method of choice for the study of the skull base and its foramina. MRI explores the cranial nerves and their vascular relationships precisely. Because of their small size, it is essential to obtain images with high spatial resolution. The MRI sequences optimize contrast between nerves and surrounding structures (cerebrospinal fluid, fat, bone structures and vessels). This chapter discusses the radiological anatomy of the cranial nerves.

  1. Nerve-pulse interactions

    SciTech Connect

    Scott, A.C.

    1982-01-01

    Some recent experimental and theoretical results on mechanisms through which individual nerve pulses can interact are reviewed. Three modes of interactions are considered: (1) interaction of pulses as they travel along a single fiber which leads to velocity dispersion; (2) propagation of pairs of pulses through a branching region leading to quantum pulse code transformations; and (3) interaction of pulses on parallel fibers through which they may form a pulse assembly. This notion is analogous to Hebb's concept of a cell assembly, but on a lower level of the neural hierarchy.

  2. Defective adrenergic responses in patients with arsenic-induced peripheral vascular disease.

    PubMed

    Lee, Chih-Hung; Chang, Huoy-Rou; Chen, Jau-Shiuh; Chen, Gwo-Shing; Yu, Hsin-Su

    2007-01-01

    Blackfoot disease is an endemic arsenic-induced peripheral vascular disease in southern Taiwan. The main pathologic feature is atherosclerosis, which may relate to imbalances of the adrenergic system. The purpose of this study is to investigate the peripheral adrenergic responses of patients with blackfoot disease. Eight patients with blackfoot disease and four age-matched healthy controls were enrolled in this study. Baseline cutaneous perfusion was measured with a laser Doppler flowmeter. The response of alpha-adrenoceptors in the cutaneous microcirculation was assessed with laser Doppler flowmetry with iontophoresis of phenylephrine into the nailfold. In vitro binding with (125)I-cyanopindolol determined beta-adrenoceptor density in lymphocytes. The cyclic adenosine monophosphate (cAMP) level at baseline and after isoproterenol stimulation reflects lymphocyte beta-adrenergic responsiveness. Results revealed persistently decreased skin perfusion in patients with blackfoot disease. In contrast, there was a transient decrease in skin perfusion in healthy controls after iontophoresis of phenylephrine. Both beta-2 receptor density and isoproterenol-stimulated cAMP levels in lymphocytes decreased. Increased peripheral alpha-adrenergic response and decreased beta-2-adrenergic response are related to increased vascular tone and result in atherosclerosis. Our findings of accentuated alpha-adrenergic response in microcirculation and decreased lymphocyte beta-2-adrenoceptor response play an important role in the pathogenesis of atherosclerosis in blackfoot disease.

  3. Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling.

    PubMed

    Sun, Fan; Ding, Xu-Ping; An, Shi-Min; Tang, Ya-Bin; Yang, Xin-Jie; Teng, Lin; Zhang, Chun; Shen, Ying; Chen, Hong-Zhuan; Zhu, Liang

    2015-01-01

    Embryonic pluripotent cells are sensitive to genotoxicity though they need more stringent genome integrity to avoid compromising multiple cell lineages and subsequent generations. However it remains unknown whether the cells are susceptible to adrenergic stress which can induce somatic cell genome lesion. We have revealed that adrenergic stress mediators cause DNA damage of the cells through the β2 adrenergic receptor/adenylate cyclase/cAMP/PKA signalling pathway involving an induction of intracellular reactive oxygen species (ROS) accumulation. The adrenergic stress agonists adrenaline, noradrenaline, and isoprenaline caused DNA damage and apoptosis of embryonic stem (ES) cells and embryonal carcinoma stem cells. The effects were mimicked by β2 receptor-coupled signalling molecules and abrogated by selective blockade of β2 receptors and inhibition of the receptor signalling pathway. RNA interference targeting β2 receptors of ES cells conferred the cells the ability to resist the DNA damage and apoptosis. In addition, adrenergic stimulation caused a consistent accumulation of ROS in the cells and the effect was abrogated by β2 receptor blockade; quenching of ROS reversed the induced DNA damage. This finding will improve the understanding of the stem cell regulatory physiology/pathophysiology in an adrenergic receptor subtype signalling mechanism. PMID:26516061

  4. Analysis of adrenergic regulation of melatonin synthesis in Siberian hamster pineal emphasizes the role of HIOMT.

    PubMed

    Ceinos, R M; Chansard, M; Revel, F; Calgari, C; Míguez, J M; Simonneaux, V

    2004-01-01

    Seasonal variations of environmental factors are translated into annual fluctuations in synthesis and release of melatonin, which in turn acts as a neuroendocrine messenger for the synchronization of annual functions. So far, most studies performed to understand the regulation of melatonin synthesis have used the non seasonal laboratory rat. It was demonstrated that nocturnal melatonin synthesis depends on alpha- and beta-adrenergic activation of the enzyme arylalkylamine N-acetyltransferase (AA-NAT). In this study, we investigated the mechanisms of melatonin synthesis in the Siberian hamster, a seasonal species with marked photoperiodic variation in melatonin peak duration and amplitude. A beta-adrenergic receptor agonist alone markedly stimulated AA-NAT activity and melatonin synthesis and release. An alpha-adrenergic receptor agonist, while having no effect per se, potentiated the beta-adrenergic stimulation of AA-NAT activity both in vitro and in vivo. Strikingly, the potentiation of AA-NAT activity did not result in a potentiation of melatonin synthesis, suggesting that the rate of melatonin production is limited downstream in the metabolic pathway, most probably at the level of hydroxyindole-O-methyltransferase (HIOMT). HIOMT presented a constitutively high activity that was not acutely (within hours) stimulated by beta-adrenergic agonist, but was rather up-regulated by chronic application of the agonist. This long-term beta-adrenergic regulation may explain the reported large photoperiodic variation of HIOMT activity that drives the photoperiodic variation in melatonin peak.

  5. α(1D)-Adrenergic receptors constitutive activity and reduced expression at the plasma membrane.

    PubMed

    García-Sáinz, J Adolfo; Romero-Ávila, M Teresa; Medina, Luz Del Carmen

    2010-01-01

    Adrenergic receptors are a heterogeneous family of the G protein-coupled receptors that mediate the actions of adrenaline and noradrenaline. Adrenergic receptors comprise three subfamilies (α(1), α(2), and β, with three members each) and the α(1D)-adrenergic receptor is one of the members of the α(1) subfamily with some interesting traits. The α(1D)-adrenergic receptor is difficult to express, seems predominantly located intracellularly, and exhibits constitutive activity. In this chapter, we will describe in detail the conditions and procedures used to determine changes in intracellular free calcium concentration which has been instrumental to define the constitutive activity of these receptors. Taking advantage of the fact that truncation of the first 79 amino acids of α(1D)-adrenergic receptors markedly increased their membrane expression, we were able to show that constitutive activity is present in receptors truncated at the amino and carboxyl termini, which indicates that such domains are dispensable for this action. Constitutive activity could be observed in cells expressing either the rat or human α(1D)-adrenergic receptor orthologs. Such constitutive activity has been observed in native rat arteries and we will discuss the possible functional implications that it might have in the regulation of blood pressure.

  6. Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling

    PubMed Central

    Sun, Fan; Ding, Xu-Ping; An, Shi-Min; Tang, Ya-Bin; Yang, Xin-Jie; Teng, Lin; Zhang, Chun; Shen, Ying; Chen, Hong-Zhuan; Zhu, Liang

    2015-01-01

    Embryonic pluripotent cells are sensitive to genotoxicity though they need more stringent genome integrity to avoid compromising multiple cell lineages and subsequent generations. However it remains unknown whether the cells are susceptible to adrenergic stress which can induce somatic cell genome lesion. We have revealed that adrenergic stress mediators cause DNA damage of the cells through the β2 adrenergic receptor/adenylate cyclase/cAMP/PKA signalling pathway involving an induction of intracellular reactive oxygen species (ROS) accumulation. The adrenergic stress agonists adrenaline, noradrenaline, and isoprenaline caused DNA damage and apoptosis of embryonic stem (ES) cells and embryonal carcinoma stem cells. The effects were mimicked by β2 receptor-coupled signalling molecules and abrogated by selective blockade of β2 receptors and inhibition of the receptor signalling pathway. RNA interference targeting β2 receptors of ES cells conferred the cells the ability to resist the DNA damage and apoptosis. In addition, adrenergic stimulation caused a consistent accumulation of ROS in the cells and the effect was abrogated by β2 receptor blockade; quenching of ROS reversed the induced DNA damage. This finding will improve the understanding of the stem cell regulatory physiology/pathophysiology in an adrenergic receptor subtype signalling mechanism. PMID:26516061

  7. Immunoanalogue of vertebrate beta-adrenergic receptor in the unicellular eukaryote Paramecium.

    PubMed

    Wiejak, Jolanta; Surmacz, Liliana; Wyroba, Elzbieta

    2002-01-01

    Cell fractionation, SDS-PAGE, quantitative Western blot, confocal immunolocalization and immunogold labelling were performed to find an interpretation of the physiological response of the unicellular eukaryote Paramecium to beta-adrenergic ligands. The 69 kDa polypeptide separated by SDS-PAGE in S2 and P2 Paramecium subcellular fractions cross-reacted with antibody directed against human beta2-adrenergic receptor. This was detected by Western blotting followed by chemiluminescent detection. Quantitative image analysis showed that beta-selective adrenergic agonist (-)-isoproterenol--previously shown to enhance phagocytic activity--evoked redistribution of the adrenergic receptor analogue from membraneous (P2) to cytosolic (S2) fraction. The relative increase in immunoreactive band intensity in S2 reached 80% and was paralleled by a 59% decrease in P2 fraction. Confocal immunofluorescence revealed beta2-adrenergic receptor sites on the cell surface and at the ridge of the cytopharynx--where nascent phagosomes are formed. This localization was confirmed by immunoelectron microscopy. These results indicate that the 69 kDa Paramecium polypeptide immunorelated to vertebrate beta2-adrenergic receptor appeared in this evolutionary ancient cell as a nutrient receptor.

  8. beta. -adrenergic relaxation of smooth muscle: differences between cells and tissues

    SciTech Connect

    Scheid, C.R.

    1987-09-01

    The present studies were carried out in an attempt to resolve the controversy about the Na/sup +/ dependence of ..beta..-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of ..beta..-adrenergic agents, including a stimulatory effect on /sup 45/Ca efflux, were dependent on the presence of a normal transmembrane Na/sup +/ gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of ..beta..-adrenergic agents was Na/sup +/ independent. Uncertainty remained as to whether these discrepancies reflected differences between cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na/sup +/ dependence of ..beta..-adrenergic relaxation. They found that elimination of a normal Na/sup +/ gradient abolished ..beta..-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of ..beta..-adrenergic relaxation may reflect inherent differences between tissues and cells.

  9. Synaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injury.

    PubMed

    Park, John; Trinh, Van Nancy; Sears-Kraxberger, Ilse; Li, Kang-Wu; Steward, Oswald; Luo, Z David

    2016-02-01

    Trigeminal nerves collecting sensory information from the orofacial area synapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at 3 weeks postinjury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states.

  10. Oculofacial Pain: Corneal Nerve Damage Leading to Pain Beyond the Eye

    PubMed Central

    Rosenthal, Perry; Borsook, David; Moulton, Eric A.

    2016-01-01

    The cornea is supplied principally by the ophthalmic branch of the trigeminal nerve and is the most densely innervated organ in the human body. Under normal conditions, the corneal nerve terminals incorporate sensors that monitor the thickness and integrity of the tear film, which are essential for meaningful vision. A disrupted tear film or direct noxious stimulation of these corneal nerves can produce discomfort or pain limited to the affected surface. Damage to these nerves can sometimes lead to a chronic neuropathic condition, where pain persists months following the initial insult, long after the nerves appear to have healed in the cornea itself following treatment. Neuropathic pain appears to persist indefinitely in a few patients. PMID:27723896

  11. Perikaryal and synaptic localization of alpha 2A-adrenergic receptor-like immunoreactivity.

    PubMed

    Aoki, C; Go, C G; Venkatesan, C; Kurose, H

    1994-07-11

    Through molecular cloning, the existence of three distinct subtypes of alpha 2-adrenergic receptors (alpha 2AR)--A, B and C--has been established and are referred to as alpha 2A AR, alpha 2B AR and alpha 2CAR. Due to limitations in pharmacological tools, it has been difficult to ascribe the role of each subtype to the central functions of alpha 2AR. In situ hybridization studies have provided valuable information regarding their distribution within brain. However, little is known about their subcellular distribution, and in particular, their pre- versus postsynaptic localization or their relation to noradrenergic neurons in the CNS. We used an antiserum that selectively recognizes the A-subtype of alpha 2AR to determine: (1) the regional distribution of the receptor within brains of rat and monkey; (2) the subcellular distribution of the receptor in locus coeruleus (LC) of rats and prefrontal cortex of monkeys; and (3) the ultrastructural relation of the receptor to noradrenergic processes in LC. Light microscopic immunocytochemistry revealed prominent immunoreactivity in LC, the brainstem regions modulating the baroreflex, the granule cell layer of the cerebellar cortex, the paraventricular and supraoptic nuclei of the hypothalamus (PVN, SON), the basal ganglia, all thalamic nuclei, the hippocampal formation and throughout cerebral cortical areas. Comparison of results obtained from rat and monkey brains revealed no apparent interspecies-differences in the regional distribution of immunoreactivity. Immunoreactivity occurred as small puncta, less than 1 micron in diameter, that cluster over neuronal perikarya. Besides these puncta, cell bodies, proximal dendrites and fine varicose processes--most likely to be axonal--of the PVN and SON and the hippocampal granule cells also exhibited homogeneously intense distribution of immunoreactivity. Subcellularly, alpha 2AAR-ir in LC and prefrontal cortex were associated with synaptic and non-synaptic plasma membrane of

  12. N-cadherin expression in palisade nerve endings of rat vellus hairs.

    PubMed

    Kaidoh, Toshiyuki; Inoué, Takao

    2008-02-01

    Palisade nerve endings (PNs) are mechanoreceptors around vellus hairs of mammals. Each lanceolate nerve ending (LN) of the PN is characterized by a sensory nerve ending symmetrically sandwiched by two processes of type II terminal Schwann cells (tSCIIs). However, the molecular mechanisms underlying the structural organization of the PN are poorly understood. Electron microscopy showed that adherens junctions appeared to adhere to the sensory nerve ending and tSCII processes, so we examined the location of the N-cadherin adhesion system in PNs of rat vellus hairs by using immunoelectron microscopy. N-cadherin localized near both ends of the cell boundary between sensory nerve ending and tSCII processes, which corresponded to the sites of adherens junctions. We further found cadherin-associated proteins, alpha- and beta-catenins, at the linings of adherens junctions. Three-dimensional reconstruction of immunoelectron microscopic serial thin sections showed four linear arrays of N-cadherin arranged longitudinally along the LN beneath the four longitudinal borders of two tSCII processes. In contrast, sensory nerve fibers just proximal to the LNs formed common unmyelinated nerve fibers, in which N-cadherin was located mainly at the mesaxon of type I terminal Schwann cells (tSCIs). These results suggest that the four linear arrays of N-cadherin-mediated junctions adhere the sensory nerve ending and tSCII processes side by side to form the characteristic structure of the LN, and the structural differences between the LNs and the proximal unmyelinated nerve fibers possibly are due to the difference in the pattern of N-cadherin expression between sensory nerve endings and tSCII or tSCI processes.

  13. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

    PubMed Central

    Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C.; Chang, Christopher J.; Montecucco, Cesare; Rigoni, Michela

    2015-01-01

    An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

  14. Retrograde axonal transport of /sup 125/I-nerve growth factor in rat ileal mesenteric nerves. Effect of streptozocin diabetes

    SciTech Connect

    Schmidt, R.E.; Plurad, S.B.; Saffitz, J.E.; Grabau, G.G.; Yip, H.K.

    1985-12-01

    The retrograde axonal transport of intravenously (i.v.) administered /sup 125/I-nerve growth factor (/sup 125/I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of /sup 125/I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of /sup 125/I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The /sup 125/I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar /sup 125/I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of /sup 125/I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of /sup 125/I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported /sup 125/I-NGF at the sites of dystrophic axonal lesions.

  15. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  16. Sports and peripheral nerve injury.

    PubMed

    Hirasawa, Y; Sakakida, K

    1983-01-01

    Peripheral nerve injury is one of the serious complications of athletic injuries; however, they have rarely been reported. According to the report by Takazawa et al., there were only 28 cases of peripheral nerve injury among 9,550 cases of sports injuries which had been treated in the previous 5 years at the clinic of the Japanese Athletic Association. The authors have encountered 1,167 cases of peripheral nerve injury during the past 18 years. Sixty-six of these cases were related to sports (5.7%). The nerves most frequently involved were: brachial plexus, radial nerve, ulnar, peroneal, and axillary nerves (in their order of frequency). The most common causes of such injuries were mountain climbing, gymnastics, and baseball. More often, peripheral nerve injury seemed to be caused by continuous compression and repeated trauma to the involved nerve. Usually it appeared as an entrapment neuropathy and the symptoms could be improved by conservative treatment. Some of the cases were complicated by fractures and surgical exploration became necessary. Results of treatment produced excellent to good improvement in 87.9% of the cases. With regard to compartment syndrome, the authors stress the importance of early and precise diagnosis and a fasciotomy.

  17. Changes in nerve- and endothelium-mediated contractile tone of the corpus cavernosum in a mouse model of pre-mature ageing.

    PubMed

    Lafuente-Sanchis, A; Triguero, D; Garcia-Pascual, A

    2014-07-01

    Erectile dysfunction (ED) is very prevalent in the older population, although the ageing-related mechanisms involved in the development of ED are poorly understood. We propose that age-induced differences in nerve- and endothelium-mediated smooth muscle contractility in the corpus cavernosum (CC) could be found between a senescent-accelerated mouse prone (SAMP8) and senescent-accelerated mouse resistant (SAMR1) strains. We analysed the changes in muscle tension induced by electrical field stimulation (EFS) or agonist addition 'in vitro', assessing nerve density (adrenergic, cholinergic and nitrergic), the expression of endothelial nitric oxide synthase (eNOS), cGMP accumulation and the distribution of interstitial cells (ICs) by immunofluorescence. We observed no change in both the nerve-dependent adrenergic excitatory contractility at physiological levels of stimulation and in the nitrergic inhibitory response in SAMP8 animals. Unlike cholinergic innervation, the density of adrenergic and nitrergic nerves increased in SAMP8 mice. In contrast, smooth muscle sensitivity to exogenous noradrenaline (NA) was slightly reduced, whereas cGMP accumulation in response to EFS and DEA/NO, and relaxations to DEA/NO and sildenafil, were not modified. No changes in the expression of eNOS and in the distribution of vimentin-positive ICs were detected in the aged animals. The ACh induced atropine-sensitive biphasic endothelium-dependent responses involved relaxation at low concentrations that turned into contractions at the highest doses. CC relaxation was mainly because of the production of NO together with some relaxant prostanoid, which did not change in SAMP8 animals. In contrast, the contractile component was considerably higher in the aged animals and it was completely inhibited by indomethacin. In conclusion, a clear imbalance towards enhanced production of contractile prostanoids from the endothelium may contribute to ED in the elderly. On the basis of these data, we

  18. Ultrasonographic Evaluation of Peripheral Nerves.

    PubMed

    Ali, Zarina S; Pisapia, Jared M; Ma, Tracy S; Zager, Eric L; Heuer, Gregory G; Khoury, Viviane

    2016-01-01

    There are a variety of imaging modalities for evaluation of peripheral nerves. Of these, ultrasonography (US) is often underused. There are several advantages of this imaging modality, including its cost-effectiveness, time-efficient assessment of long segments of peripheral nerves, ability to perform dynamic maneuvers, lack of contraindications, portability, and noninvasiveness. It can provide diagnostic information that cannot be obtained by electrophysiologic or, in some cases, magnetic resonance imaging studies. Ideally, the neurosurgeon can use US as a diagnostic adjunct in the preoperative assessment of a patient with traumatic, neoplastic, infective, or compressive nerve injury. Perhaps its most unique use is in intraoperative surgical planning. In this article, a brief description of normal US nerve anatomy is presented followed by a description of the US appearance of peripheral nerve disease caused by trauma, tumor, infection, and entrapment.

  19. Peripheral nerve conduits: technology update

    PubMed Central

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  20. Adenylyl Cyclase Anchoring by a Kinase Anchor Protein AKAP5 (AKAP79/150) Is Important for Postsynaptic β-Adrenergic Signaling*

    PubMed Central

    Zhang, Mingxu; Patriarchi, Tommaso; Stein, Ivar S.; Qian, Hai; Matt, Lucas; Nguyen, Minh; Xiang, Yang K.; Hell, Johannes W.

    2013-01-01

    Recent evidence indicates that the A kinase anchor protein AKAP5 (AKAP79/150) interacts not only with PKA but also with various adenylyl cyclase (AC) isoforms. However, the physiological relevance of AC-AKAP5 binding is largely unexplored. We now show that postsynaptic targeting of AC by AKAP5 is important for phosphorylation of the AMPA-type glutamate receptor subunit GluA1 on Ser-845 by PKA and for synaptic plasticity. Phosphorylation of GluA1 on Ser-845 is strongly reduced (by 70%) under basal conditions in AKAP5 KO mice but not at all in D36 mice, in which the PKA binding site of AKAP5 (i.e. the C-terminal 36 residues) has been deleted without affecting AC association with GluA1. The increase in Ser-845 phosphorylation upon β-adrenergic stimulation is much more severely impaired in AKAP5 KO than in D36 mice. In parallel, long term potentiation induced by a 5-Hz/180-s tetanus, which mimics the endogenous θ-rhythm and depends on β-adrenergic stimulation, is only modestly affected in acute forebrain slices from D36 mice but completely abrogated in AKAP5 KO mice. Accordingly, anchoring of not only PKA but also AC by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity. PMID:23649627

  1. Adenylyl cyclase anchoring by a kinase anchor protein AKAP5 (AKAP79/150) is important for postsynaptic β-adrenergic signaling.

    PubMed

    Zhang, Mingxu; Patriarchi, Tommaso; Stein, Ivar S; Qian, Hai; Matt, Lucas; Nguyen, Minh; Xiang, Yang K; Hell, Johannes W

    2013-06-14

    Recent evidence indicates that the A kinase anchor protein AKAP5 (AKAP79/150) interacts not only with PKA but also with various adenylyl cyclase (AC) isoforms. However, the physiological relevance of AC-AKAP5 binding is largely unexplored. We now show that postsynaptic targeting of AC by AKAP5 is important for phosphorylation of the AMPA-type glutamate receptor subunit GluA1 on Ser-845 by PKA and for synaptic plasticity. Phosphorylation of GluA1 on Ser-845 is strongly reduced (by 70%) under basal conditions in AKAP5 KO mice but not at all in D36 mice, in which the PKA binding site of AKAP5 (i.e. the C-terminal 36 residues) has been deleted without affecting AC association with GluA1. The increase in Ser-845 phosphorylation upon β-adrenergic stimulation is much more severely impaired in AKAP5 KO than in D36 mice. In parallel, long term potentiation induced by a 5-Hz/180-s tetanus, which mimics the endogenous θ-rhythm and depends on β-adrenergic stimulation, is only modestly affected in acute forebrain slices from D36 mice but completely abrogated in AKAP5 KO mice. Accordingly, anchoring of not only PKA but also AC by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity.

  2. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

    SciTech Connect

    Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.; Greden, J.F.; Smith, C.B.

    1981-12-01

    The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors.

  3. Cloning and expression of a human kidney cDNA for an /alpha//sub 2/-adrenergic receptor subtype

    SciTech Connect

    Regan, J.W.; Kobilka, T.S.; Yang-Feng, T.L.; Caron, M.G.; Lefkowitz, R.J.; Kobilka, B.K.

    1988-09-01

    An /alpha//sub 2/-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet /alpha//sub 2/-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet /alpha//sub 2/-adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the /alpha//sub 2/-adrenergic ligand (/sup 3/H)rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the /alpha//sub 2/B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet /alpha//sub 2/-adrenergic receptor (/alpha//sub 2/A) lies on chromosome 10. This ability to express the receptor in mammalian cells, free of other adrenergic receptor subtypes, should help in developing more selective /alpha/-adrenergic ligands.

  4. Peripheral nerve blocks for distal extremity surgery.

    PubMed

    Offierski, Chris

    2013-10-01

    Peripheral nerve block is well suited for distal extremity surgery. Blocking the nerves at the distal extremity is easily done. It does not require ultrasound or stimulators to identify the nerve. Blocking nerves in the distal extremity is safe with low risk of toxicity. The effect of the nerve block is limited to the distribution of the nerve. The distal nerves in the lower extremity are sensory branches of the sciatic nerve. This provides a sensory block only. This has the advantage of allowing the patient to actively contract tendons in the foot and ambulate more quickly after surgery. PMID:24093651

  5. The PLATO V Terminal.

    ERIC Educational Resources Information Center

    Stifle, J. E.

    This report provides a detailed description of the architecture and programming of the PLATO V terminal, which contains an 8080 microprocessor and is capable of being operated by programs located in a host computer. The terminal contains 8k of memory for storing local programs, a 4k ROM resident program which supervises terminal operation, a 2k…

  6. CAI Terminal Characteristics.

    ERIC Educational Resources Information Center

    Braun, Peter

    The bewildering number of available terminals which are offered to CAI users presents a rather formidable problem of which one to choose. This article surveys what appear to be evolving standards for terminals. The usefulness of these terminals for CAI purposes is discussed, together with the best known prototype exhibiting the particular feature.…

  7. Adrenergic signaling in teleost fish liver, a challenging path.

    PubMed

    Fabbri, Elena; Moon, Thomas W

    2016-09-01

    Adrenergic receptors or adrenoceptors (ARs) belong to the huge family of G-protein coupled receptors (GPCRs) that have been well characterized in mammals primarily because of their importance as therapeutic drug targets. ARs are found across vertebrates and this review examines the path to identify and characterize these receptors in fish with emphasis on hepatic metabolism. The absence of reliable and specific pharmacological agents led investigators to define the fish hepatic AR system as relying solely on a β2-AR, cAMP-dependent signaling transduction pathway. The use of calcium-radiometric imaging, purified membranes for ligand-binding studies, and perifused rather than static cultured fish hepatocytes, unequivocally demonstrated that both α1- and β2-AR signaling systems existed in the fish liver consistent with studies in mammals. Additionally, the use of molecular tools and phylogenetic analysis clearly demonstrated the existence of multiple AR-types and -subtypes in hepatic and other tissues of a number of fish species. This review also examines the use of β-blockers as pharmaceuticals and how these drugs that are now in the aquatic environment may be impacting aquatic species including fish and some invertebrates. Clearly there is a large conservation of structure and function within the AR system of vertebrates but there remain a number of key questions that need to be addressed before a clear understanding of these systems can be resolved. PMID:26482086

  8. Postnatal development of adrenergic responsiveness in the rabbit heart.

    PubMed

    Feng, Z P; Dryden, W F; Gordon, T

    1989-08-01

    It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 +/- 7 to 175 +/- 33% above control twitch tension between 3 and 21 days of age; this is followed by a decrease to 68 +/- 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 +/- 2.3 to 56.6 +/- 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 +/- 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.

  9. Adrenergic signaling in teleost fish liver, a challenging path.

    PubMed

    Fabbri, Elena; Moon, Thomas W

    2016-09-01

    Adrenergic receptors or adrenoceptors (ARs) belong to the huge family of G-protein coupled receptors (GPCRs) that have been well characterized in mammals primarily because of their importance as therapeutic drug targets. ARs are found across vertebrates and this review examines the path to identify and characterize these receptors in fish with emphasis on hepatic metabolism. The absence of reliable and specific pharmacological agents led investigators to define the fish hepatic AR system as relying solely on a β2-AR, cAMP-dependent signaling transduction pathway. The use of calcium-radiometric imaging, purified membranes for ligand-binding studies, and perifused rather than static cultured fish hepatocytes, unequivocally demonstrated that both α1- and β2-AR signaling systems existed in the fish liver consistent with studies in mammals. Additionally, the use of molecular tools and phylogenetic analysis clearly demonstrated the existence of multiple AR-types and -subtypes in hepatic and other tissues of a number of fish species. This review also examines the use of β-blockers as pharmaceuticals and how these drugs that are now in the aquatic environment may be impacting aquatic species including fish and some invertebrates. Clearly there is a large conservation of structure and function within the AR system of vertebrates but there remain a number of key questions that need to be addressed before a clear understanding of these systems can be resolved.

  10. Optodynamic simulation of β-adrenergic receptor signalling

    PubMed Central

    Siuda, Edward R.; McCall, Jordan G.; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J.; Anderson, Sonya L.; Planer, William J.; Rogers, John A.; Bruchas, Michael R.

    2015-01-01

    Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo. PMID:26412387

  11. Adrenergic activation attenuates astrocyte swelling induced by hypotonicity and neurotrauma.

    PubMed

    Vardjan, Nina; Horvat, Anemari; Anderson, Jamie E; Yu, Dou; Croom, Deborah; Zeng, Xiang; Lužnik, Zala; Kreft, Marko; Teng, Yang D; Kirov, Sergei A; Zorec, Robert

    2016-06-01

    Edema in the central nervous system can rapidly result in life-threatening complications. Vasogenic edema is clinically manageable, but there is no established medical treatment for cytotoxic edema, which affects astrocytes and is a primary trigger of acute post-traumatic neuronal death. To test the hypothesis that adrenergic receptor agonists, including the stress stimulus epinephrine protects neural parenchyma from damage, we characterized its effects on hypotonicity-induced cellular edema in cortical astrocytes by in vivo and in vitro imaging. After epinephrine administration, hypotonicity-induced swelling of astrocytes was markedly reduced and cytosolic 3'-5'-cyclic adenosine monophosphate (cAMP) was increased, as shown by a fluorescence resonance energy transfer nanosensor. Although, the kinetics of epinephrine-induced cAMP signaling was slowed in primary cortical astrocytes exposed to hypotonicity, the swelling reduction by epinephrine was associated with an attenuated hypotonicity-induced cytosolic Ca(2+) excitability, which may be the key to prevent astrocyte swelling. Furthermore, in a rat model of spinal cord injury, epinephrine applied locally markedly reduced neural edema around the contusion epicenter. These findings reveal new targets for the treatment of cellular edema in the central nervous system. PMID:27018061

  12. Pharmacogenetics of the β2-Adrenergic Receptor Gene

    PubMed Central

    Ortega, Victor E.; Hawkins, Gregory A.; Peters, Stephen P.; Bleecker, Eugene R.

    2009-01-01

    Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time. PMID:17996583

  13. Molecular evolution of the mammalian alpha 2B adrenergic receptor.

    PubMed

    Madsen, Ole; Willemsen, Diederik; Ursing, Björn M; Arnason, Ulfur; de Jong, Wilfried W

    2002-12-01

    The alpha 2B adrenergic receptor (A2AB) is a heptahelical G protein-coupled receptor for catecholamines. We compared the almost complete coding region (about 1,175 bp) of the A2AB gene from 48 mammalian species, including eight newly determined sequences, representing all the 18 eutherian and two marsupial orders. Comparison of the encoded proteins reveals that residues thought to be involved in agonist binding are highly conserved, as are the regions playing a role in G protein-coupling. The three extracellular loops are generally more variable than the transmembrane domains and two of the intracellular loops, indicating a lower functional constraint. However, the greatest variation is observed in the very long, third intracellular loop, where only a few residues and a polyglutamyl tract are preserved. Although this polyglutamyl domain displays a great variation in length, its presence in all described A2ABs confirms its proposed role in agonist-dependent phosphorylation of the third intracellular loop. Phylogenetic analyses of the A2AB data set, including Bayesian methods, recognized the superordinal clades Afrotheria, Laurasiatheria, and Euarchontoglires, in agreement with recent molecular evidence, albeit with lower support. Within Afrotheria, A2AB strongly supports the paenungulate clade and the association of the continental African otter shrew with Malagasy tenrecs. Among Laurasiatheria, A2AB confirms the nesting of whales within the artiodactyls, as a sister group to hippopotamus. Within the Euarchontoglires, there is constant support for rodent monophyly. PMID:12446807

  14. Modulation of haemocyte phagocytic and antibacterial activity by alpha-adrenergic receptor in scallop Chlamys farreri.

    PubMed

    Zhou, Zhi; Jiang, Qiufeng; Wang, Mengqiang; Yue, Feng; Wang, Lingling; Wang, Leilei; Li, Fengmei; Liu, Rui; Song, Linsheng

    2013-09-01

    The adrenergic receptors are a class of G protein-coupled receptors, through which norepinephrine and epinephrine trigger the second messenger to modulate the immune response in immunocytes of vertebrate. In the present study, a gene coding the homologue of α-adrenergic receptor was identified from scallop Chlamys farreri (designated CfαAR). Its deduced protein comprised 318 amino acids, and contained a conserved 7tm_1 domain. After CfαAR protein was expressed in the HEK293 cells, the stimulation of octopamine, tyramine, epinephrine and isoprenaline (β-adrenergic receptor agonist) did not change significantly the intracellular cAMP concentration, whereas the stimulation of norepinephrine and phenylephrine (α-adrenergic receptor agonist) lowered significantly the cAMP level to 0.52 and 0.84 pmol μl(-1) (P < 0.05), respectively. The CfαAR transcripts were ubiquitously detected in the tested tissues including haemocytes, adductor muscle, kidney, hepatopancreas, gill, gonad and mantle, with the highest expression in the gill. The expression level of CfαAR mRNA decreased significantly (0.21-fold, P < 0.05) at 3 h after the challenge of bacteria Vibrio anguillarum. Then, it began to increase (4.74-fold, P < 0.05) at 12 h, and reached the highest level (4.92-fold, P < 0.05) at 24 h after bacteria challenge. The addition of α-adrenergic receptor agonist to the primary scallop haemocytes repressed significantly the increase of phagocytic and antibacterial activity induced by LPS stimulation, while the induction was reverted by the addition of α-adrenergic receptor antagonist. These results collectively suggested that α-adrenergic receptor could be regulated dynamically in the transcriptional level during the immune response, and it could modulate the haemocyte phagocytic and antibacterial function through the second messenger cAMP, which might be requisite for pathogen elimination and the homeostasis maintenance in scallop.

  15. Ghrelin-induced hypophagia is mediated by the β2 adrenergic receptor in chicken.

    PubMed

    Zendehdel, Morteza; Hassanpour, Shahin

    2014-09-01

    The purpose of this study was to examine the effects of intracerebroventricular injection of metoprolol (a β1 adrenergic receptor antagonist), ICI 118,551 (a β2 adrenergic receptor antagonist), and SR 59230R (a β3 adrenergic receptor antagonist) on ghrelin-induced food and water intake by 3-h food-deprived (FD3) cockerels. The chickens were randomly allocated to 4 treatment groups with 8 replicates in each group. A cannula was surgically implanted into the lateral ventricle of the brain. In experiment 1, chickens received the β1 adrenergic receptor antagonist (24 nmol) before injection of the ghrelin (0.6 nmol). In experiment 2, chickens received the β2 adrenergic receptor antagonist (5 nmol) before injection of the ghrelin (0.6 nmol). In experiment 3, birds were injected with ghrelin (0.6 nmol) after the β3 adrenergic receptor antagonist (20 nmol). Cumulative food and water intake were recorded 3-h post injection and analyzed by two-way analysis of variance. According to the results, ghrelin injection reduced food and water intake by broiler cockerels (p≤0.05). The effect of ghrelin on food intake was significantly attenuated by pretreatment with the β2 receptor antagonist (p≤0.05). Furthermore, the β2 receptor antagonist had no effect on water intake induced by ghrelin. Also, pretreatment with the β1 and β3 receptors antagonists had no effect on ghrelin-induced food and water intake. These results suggest that the effect of ghrelin on cumulative food intake by cockerels is mediated via β2 adrenergic receptors.

  16. β-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum.

    PubMed

    Lamkin, Donald M; Ho, Hsin-Yun; Ong, Tiffany H; Kawanishi, Carly K; Stoffers, Victoria L; Ahlawat, Nivedita; Ma, Jeffrey C Y; Arevalo, Jesusa M G; Cole, Steve W; Sloan, Erica K

    2016-10-01

    β-Adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one pre-defined category of the M1-M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1-M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  17. Alpha-adrenergic stimulation of thermogenesis in a rat kangaroo (Marsupialia, Bettongia gaimardi).

    PubMed

    Ye, J M; Edwards, S J; Rose, R W; Steen, J T; Clark, M G; Colquhoun, E Q

    1996-09-01

    The Tasmanian bettong (Bettongia gaimardi) is a small rat kangaroo without detectable brown adipose tissue (BAT). In view of our previous findings of norepinephrine-mediated increase in O2 consumption (Vo2) in the perfused hindlimb of this species, the present study examined the effect of alpha-adrenoceptors on the thermogenesis of conscious bettongs at rest by infusing adrenergic agents via an indwelling catheter in the tail vein. The resting Vo2 was 22.9 +/- 1.9 mmol.kg-1.h-1. Norepinephrine (10-80 micrograms.kg-1.min-1) stimulated Vo2 in a dose-dependent manner with the maximal increment of 46.7%. Naphazoline (an alpha 1,alpha 2-adrenergic agonist) and phenylephrine (an alpha 1-adrenergic agonist) also elicited increases in Vo2 with maximal values of 29.6 and 34.8%, respectively. In contrast, the alpha 2-adrenergic agonist clonidine had no significant effects. Both alpha- and beta-adrenergic blockers were used to antagonize the submaximal increase in Vo2 elicited by norepinephrine. As a dose of 10 micrograms.kg-1.min-1, the alpha-adrenergic blocker phentolamine abolished the effects of naphazoline and phenylephrine and reduced norepinephrine-induced Vo2 by 45.5%. The beta-adrenergic blocker propranolol inhibited the norepinephrine-induced Vo2 by 58.8% at 20 micrograms.kg-1.min-1. A combination of the two antagonists blocked 82.5% of the norepinephrine-induced Vo2. Pretreatment of the animal with indomethacin (1 mg/kg), a known inhibitor of prostaglandin cyclooxygenase, had no effect on phenylephrine-elicited Vo2. Taken together, these results indicate that alpha 1-adrenoceptors are directly involved in norepinephrine-induced thermogenesis in non-BAT tissue(s).

  18. Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

    SciTech Connect

    Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

    1989-06-01

    The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of (125I)cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.

  19. Recent advances in nerve tissue engineering.

    PubMed

    Zhang, Bill G X; Quigley, Anita F; Myers, Damian E; Wallace, Gordon G; Kapsa, Robert M I; Choong, Peter F M

    2014-04-01

    Nerve injury secondary to trauma, neurological disease or tumor excision presents a challenge for surgical reconstruction. Current practice for nerve repair involves autologous nerve transplantation, which is associated with significant donor-site morbidity and other complications. Previously artificial nerve conduits made from polycaprolactone, polyglycolic acid and collagen were approved by the FDA (USA) for nerve repair. More recently, there have been significant advances in nerve conduit design that better address the requirements of nerve regrowth. Innovations in materials science, nanotechnology, and biology open the way for the synthesis of new generation nerve repair conduits that address issues currently faced in nerve repair and regeneration. This review discusses recent innovations in this area, including the use of nanotechnology to improve the design of nerve conduits and to enhance nerve regeneration.

  20. Topography and landmarks for the nerve supply to the levator ani and its relevance to pelvic floor pathologies.

    PubMed

    Loukas, Marios; Joseph, Shamfa; Etienne, Denzil; Linganna, Sanjay; Hallner, Barry; Tubbs, R Shane

    2016-05-01

    The aim of this study was to explore the anatomical variations of the nerve to the levator ani (LA) and to relate these findings to LA dysfunction. One hundred fixed human female cadavers were dissected using transabdominal, gluteal, and perineal approaches, resulting in two hundred dissections of the sacral plexus. The pudendal nerve and the sacral nerve roots were traced from their origin at the sacral foramina to their termination. All nerves contributing to the innervation of the LA were considered to be the nerve to the LA. Based on the spinal nerve components, the nerve to the LA was classified into the following categories: 50% (n = 100) originated from S4 and S5 (type I); 19% (n = 38) originated from S5 (type II); 16% (n = 32) originated from S4 (type III); 11% (n = 22) originated from S3 and S4 (type IV); 4% (n = 8) originated from S3, S4, and S5 (type V). Two patterns of nerve termination were observed. In 42% of specimens, the nerve to the LA penetrated the coccygeus muscle and assumed an external position along the inferior surface of the LA muscle. In the remaining 58% of specimens, the nerve crossed the superior surface of the coccygeus muscle and continued along the superior surface of the iliococcygeus muscle. Damage to the nerve to LA has been associated with various pathologies. In order to minimize injuries during surgical procedures, a thorough understanding of the course and variations of the nerve to the LA is extremely important.

  1. Effects of a laminin peptide (YIGSR) immobilized on crab-tendon chitosan tubes on nerve regeneration.

    PubMed

    Itoh, Soichiro; Matsuda, Atsushi; Kobayashi, Hisatoshi; Ichinose, Shizuko; Shinomiya, Kenichi; Tanaka, Junzo

    2005-05-01

    Thiolated and nonthiolated hydroxyapatite-coated crab-tendon chitosan (t-chitosan/HAp-SH and t-chitosan/HAp, respectively) tubes, both alone and conjugated with CDPGYIGSR (YIGSR) peptide, were compared, in order to determine their biocompatibility and efficacy as nerve conduits. YIGSR peptide was adsorbed on the t-chitosan/HAp (HAp) tubes, and covalently bound on the t-chitosan/HAp-SH (HAp-SH) tubes (Y/HAp and Y/HAp-SH tubes, respectively). HAp, HAp-SH, Y/HAp, or Y/HAp-SH tubes measuring 15 mm were bridge grafted into the sciatic nerve of SD rats. Grafting of 15-mm-long Type I atelocollagen tubes and isografting of sciatic nerves were also carried out (N = 6 in each group). After 12 weeks, evoked muscle action potentials were recorded to calculate the terminal latency quotient. Histological observation and analysis of myelinated axons were also carried out. Nerve-tissue regeneration did not occur directly on the tubes' surfaces in the YIGSR peptide-unconjugated groups. Transplantation of YIGSR-conjugated tubes, however, gave rise to regenerated nerve tissue attached to thin layers of epineurium-like structure formed on the inner-tube surface. Histological and electrophysiological analyses suggested that although thiolation retards nerve-tissue regeneration, adsorbed YIGSR, and, to a lesser extent, peptide that had been covalently bound onto the tube surfaces, enhance nerve regeneration, promoting sprouting from the proximal nerve stump and bridging of regenerated axons throughout the tube.

  2. Adrenalectomy mediated alterations in adrenergic activation of adenylate cyclase in rat liver

    SciTech Connect

    El-Refai, M.; Chan, T.

    1986-05-01

    Adrenalectomy caused a large increase in the number of ..beta..-adrenergic binding sites on liver plasma membranes as measured by /sup 125/I-iodocyanopindolol (22 and 102 fmol/mg protein for control and adrenalectomized (ADX) rats). Concomitantly an increase in the number of binding sites for /sup 3/H-yohimbine was also observed (104 and 175 fmol/mg protein for control and adx membranes). Epinephrine-stimulated increase in cyclic AMP accumulation in isolated hepatocytes were greater in cells from ADX rats. This increase in ..beta..-adrenergic mediated action was much less than what may be expected as a result of the increase in the ..beta..-adrenergic binding in ADX membranes. In addition phenoxybenzamine (10 ..mu..M) further augmented this action of epinephrine in both control and ADX cells. To test the hypothesis that the increase in the number of the inhibitory ..cap alpha../sub 2/-adrenergic receptors in adrenalectomy is responsible for the muted ..beta..-adrenergic response, the authors injected rats with pertussis toxin (PT). This treatment may cause the in vivo ribosylation of the inhibitory binding protein (Ni). Adenylate cyclase (AC) activity in liver plasma membranes prepared from treated and untreated animals was measured. In contrast with control rats, treatment of ADX rats with PT resulted in a significant increase in the basal activity of AC (5.5 and 7.7 pmol/mg protein/min for untreated and treated rats respectively). Isoproterenol (10 ..mu..M), caused AC activity to increase to 6.5 and 8.4 pmol/mg protein/min for membranes obtained from ADX untreated and ADX treated rats respectively. The ..cap alpha..-adrenergic antagonists had no significant effect on the ..beta..-adrenergic-mediated activation of AC in liver plasma membranes from PT treated control and ADX rats. The authors conclude that the ..beta..-adrenergic activation of AC is attenuated by Ni protein both directly and as a result of activation of ..cap alpha..-adrenergic receptors.

  3. Molecular mechanisms of nerve block by local anesthetics.

    PubMed

    Strichartz, G

    1976-10-01

    block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics...

  4. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  5. alpha-1 Adrenergic receptors stimulation induces the proliferation of neural progenitor cells in vitro.

    PubMed

    Hiramoto, Takeshi; Ihara, Yoshiaki; Watanabe, Yasuhiro

    2006-11-01

    The proliferation of neural progenitor cells (NPCs) is regulated by classical neurotransmitters such as dopamine, serotonin and acetylcholine, via its own receptors. Previous studies have reported that the depletion of L-norepinephrine decreases the proliferation of NPCs in the adult rat hippocampus and it has been suggested that L-norepinephrine regulates the proliferation of NPCs. However, it remains unknown whether or not adrenergic receptors are involved in the increased proliferation of NPCs. In the present study, an MTT cell proliferation assay was carried out in order to investigate the roles played by adrenergic receptors in the proliferation of NPCs. We demonstrated that L-epinephrine enhanced the proliferation of embryonic NPCs in vitro. In addition, the alpha-1 adrenergic receptor agonist L-phenylephrine was found to enhance the proliferation of NPCs, whereas an alpha-adrenergic antagonist and selective alpha-1 antagonists significantly inhibited cell proliferation increases induced by L-epinephrine and L-phenylephrine. These results suggest that stimulation with alpha-1 adrenergic receptors induces the proliferation of embryonic NPCs.

  6. Effects of adrenergic agents on the expression of zebrafish (Danio rerio) vitellogenin Ao1

    SciTech Connect

    Yin Naida; Jin Xia; He Jiangyan; Yin Zhan

    2009-07-01

    Teleost vitellogenins (VTGs) are large multidomain apolipoproteins, traditionally considered to be estrogen-responsive precursors of the major egg yolk proteins, expressed and synthesized mainly in hepatic tissue. The inducibility of VTGs has made them one of the most frequently used in vivo and in vitro biomarkers of exposure to estrogen-active substances. A significant level of zebrafish vtgAo1, a major estrogen responsive form, has been unexpectedly found in heart tissue in our present studies. Our studies on zebrafish cardiomyopathy, caused by adrenergic agonist treatment, suggest a similar protective function of the cardiac expressed vtgAo1. We hypothesize that its function is to unload surplus intracellular lipids in cardiomyocytes for 'reverse triglyceride transportation' similar to that found in lipid transport proteins in mammals. Our results also demonstrated that zebrafish vtgAo1 mRNA expression in heart can be suppressed by both {alpha}-adrenergic agonist, phenylephrine (PE) and {beta}-adrenergic agonist, isoproterenol (ISO). Furthermore, the strong stimulation of zebrafish vtgAo1 expression in plasma induced by the {beta}-adrenergic antagonist, MOXIsylyl, was detected by Enzyme-Linked ImmunoSorbent Assay (ELISA). Such stimulation cannot be suppressed by taMOXIfen, an antagonist to estrogen receptors. Thus, our present data indicate that the production of teleost VTG in vivo can be regulated not only by estrogenic agents, but by adrenergic signals as well.

  7. Impact of the Tamsulosin in Alpha Adrenergic Receptor of Airways at Patients with Increased Bronchial Reactibility

    PubMed Central

    Mustafa, Lirim; Ilazi, Ali; Dauti, Arta; Islami, Pellumb; Kastrati, Bashkim; Islami, Hilmi

    2015-01-01

    Objective: In this work, effect of tamsulosin as antagonist of alpha1A and alpha1B adrenergic receptor and effect of agonists of beta2 adrenergic receptor–salbutamol in patients with increased bronchial reactibility was studied. Methods: Parameters of the lung function are determined with Body plethysmography six (6) hours after administration of tamsulosin. Raw and ITGV were registered and specific resistance (SRaw) was calculated as well. Tamsulosin was administered in per os manner as a preparation in the shape of the capsules with a brand name of “Prolosin”, produced by Niche Generics Limited, Hitchin, Herts. Results: After six (6) hours of administration of tamsulosin, results gained indicate that blockage of alpha1A and alpha1B-adrenergic receptor (0.8 mg per os) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in comparison to the check-up that has inhaled salbutamol agonist of adrenergic beta2 receptor (2 inh. x 0.2 mg), (p < 0.05). Blood pressure suffered no significant decrease following administration of the 0.8 mg dose of tamsulosin. Conclusion: This suggests that even after six hours of administration of tamsulosin, and determining of lung function parameters, the activity of alpha1A and alpha1B-adrenergic receptor in the smooth bronchial musculature has not changed in patients with increased bronchial reactibility. PMID:26543414

  8. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway. PMID:26820076

  9. Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed.

    PubMed

    Tamaki, Chihiro; Nawa, Hideki; Takatori, Shingo; Oda, Sakiko; Sendo, Toshiaki; Zamami, Yoshito; Kawasaki, Hiromu

    2012-01-01

    An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 µM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB(1))-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB(1)-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.

  10. Solitary fibrous tumour of the vagus nerve.

    PubMed

    Scholsem, Martin; Scholtes, Felix

    2012-04-01

    We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.

  11. Management of traumatic facial nerve injuries.

    PubMed

    Greywoode, Jewel D; Ho, Hao H; Artz, Gregory J; Heffelfinger, Ryan N

    2010-12-01

    Management of facial nerve injuries requires knowledge and skills that should be in every facial plastic surgeon's armamentarium. This article will briefly review the anatomy of the facial nerve, discuss the assessment of facial nerve injury, and describe the management of facial nerve injury after soft tissue trauma. PMID:21086238

  12. Beta-2-adrenergic receptor polymorphisms in cystic fibrosis

    PubMed Central

    Steagall, Wendy K.; Barrow, Bethany J.; Glasgow, Connie G.; Mendoza, Jennifer Woo; Ehrmantraut, Mary; Lin, Jing-Ping; Insel, Paul A.; Moss, Joel

    2010-01-01

    Objectives Cystic fibrosis (CF), an autosomal recessive disease affecting the lung, pancreas, gut, liver, and reproductive tract, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cyclic adenosine 3′, 5′ monophosphate-regulated chloride channel. The variability of disease progression among patients with CF suggests effects of genetic modifiers of disease. Beta-2 adrenergic receptors (β2AR), which are abundant in airway epithelial cells, accelerate the formation of cyclic adenosine 3′, 5′ monophosphate, which can modulate CFTR activity and affect smooth muscle contractility. We tested the hypothesis that genetic variants of the β2AR gene, which have been shown to influence receptor desensitization, are more frequent in patients than in controls. Methods We genotyped 130 adult CF patients and 1 : 1 age-matched, sex-matched, and ethnicity-matched normal volunteers for Gly16Arg and Gln27Glu β2AR. Results We found that CF patients were more likely than controls to be Gly16 homozygotes (48 and 32%, respectively) (P < 0.01) and Glu27 homozygotes (29 and 10%, respectively) (P < 0.01). Conclusions Our results, showing a higher frequency of Gly16 and Glu27 β2AR alleles in adult CF patients than in the control population, contrast with data from children with CF, who are reported to have lower frequency of Gly16 and similar frequency of G1u27, and with data from young adults with CF, who showed no differences in frequencies of β2AR variants. The Gly16Glu27 variant of β2AR may have properties that lead to enhanced β2AR function, resulting in the upregulation of CFTR activity and the improvement of CF disease. PMID:17502834

  13. Nerve Transfers for the Restoration of Wrist, Finger, and Thumb Extension After High Radial Nerve Injury.

    PubMed

    Pet, Mitchell A; Lipira, Angelo B; Ko, Jason H

    2016-05-01

    High radial nerve injury is a common pattern of peripheral nerve injury most often associated with orthopedic trauma. Nerve transfers to the wrist and finger extensors, often from the median nerve, offer several advantages when compared to nerve repair or grafting and tendon transfer. In this article, we discuss the forearm anatomy pertinent to performing these nerve transfers and review the literature surrounding nerve transfers for wrist, finger, and thumb extension. A suggested algorithm for management of acute traumatic high radial nerve palsy is offered, and our preferred surgical technique for treatment of high radial nerve palsy is provided. PMID:27094891

  14. [Nerve-sparing radical prostatectomy].

    PubMed

    Okada, K; Tada, M; Nakano, A; Konno, T

    1988-04-01

    The neuroanatomy of the pelvic space was studied in order to clarify the course of cavernous nerves responsible for erectile function. The cavernous nerves travel along the dorsolateral portion at the base toward the apex of the prostate, then penetrate urogenital diaphragm at the lateral aspect of the membranous urethra. According to the anatomical findings, nerve-sparing radical prostatectomy was performed through the antegrade approach in 28 patients with prostate cancer. No significant surgical complications were encountered in the present series. Of the 28, evaluable cases were limited to 22 in terms of erection. Fifteen patients (68%) recovered their erectile function after nerve-sparing surgery. Therefore, the present surgical technique seems to be effective for the preservation of male sexual function following radical pelvic surgery.

  15. Schwannomatosis of Cervical Vagus Nerve

    PubMed Central

    Sasi, M. P.

    2016-01-01

    Cervical vagal schwannoma is a rare entity among lesions presenting as a neck mass. They are usually slow-growing benign lesions closely associated with the vagus nerve. They are usually solitary and asymptomatic. Multiple schwannomas occurring in patients without neurofibromatosis (NF) are rare and have recently been referred to as schwannomatosis. Here, we present a case of a neck mass that had imaging features suggestive of vagal schwannoma and was operated upon. Intraoperatively, it was discovered to be a case of multiple vagal cervical schwannoma, all directly related to the right vagus nerve, and could be resected from the nerve in toto preserving the function of the vagus nerve. Final HPR confirmed our pre-op suspicion of vagal schwannomatosis.

  16. Ion Channels in Nerve Membranes

    ERIC Educational Resources Information Center

    Ehrenstein, Gerald

    1976-01-01

    Discusses research that indicates that nerve membranes, which play a key role in the conduction of impulses, are traversed by protein channels with ion pathways opened and closed by the membrane electric field. (Author/MLH)

  17. Anatomical basis of neuropathies and damage to the ilioinguinal nerve during repairs of groin hernias. (about 100 dissections).

    PubMed

    Ndiaye, A; Diop, M; Ndoye, J M; Konaté, I; Ndiaye, A I; Mané, L; Nazarian, S; Dia, A

    2007-12-01

    Surgical access to the inguinal region, notably during hernia repairs, exposes the ilioinguinal nerve to the risk of damage at the origin of the neuralgia. The incidence of these post-operative neuropathies and their medicolegal consequences justify this study about the anatomical variations of the ilioinguinal nerve. With the aim of preventing its damage during repairs of groin hernias and identifying the factors of onset of chronic spontaneous neuropathy of the ilioinguinal nerve, we dissected 100 inguinal regions of 51 fresh adult corpses. The nerve was absent in seven cases and double in one case. Out of the 94 ilioinguinal nerves observed, we analyzed the path in relation to the inguinal ligament and the connections with the walls of the inguinal canal and its content. The ilioinguinal nerve travels along the superficial surface of the internal oblique muscle, passing on average 1.015 cm from the inguinal ligament. In one case, the fibers of the internal oblique muscle spanned it in several places. The nerve was antero-funicular in 78.72% of cases and perforated the fascia of the external oblique in 28.72% of cases. The terminal division took place in the inguinal canal in 86% of cases, with terminal branches that sometimes perforated the fascia of the external oblique. These results enabled us to better understand the etiopathogenic aspects of certain neuropathies of the groin and to propose techniques useful for the protection of the nerve during repairs of groin hernias.

  18. Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.

    PubMed

    Hodges, Gary J; Traeger, J Andrew; Tang, Tri; Kosiba, Wojciech A; Zhao, Kun; Johnson, John M

    2007-07-01

    Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.

  19. Optic Nerve Monitoring

    PubMed Central

    Schumann, Paul; Kokemüller, Horst; Tavassol, Frank; Lindhorst, Daniel; Lemound, Juliana; Essig, Harald; Rücker, Martin; Gellrich, Nils-Claudius

    2013-01-01

    Orbital and anterior skull base surgery is generally performed close to the prechiasmatic visual pathway, and clear strategies for detecting and handling visual pathway damage are essential. To overcome the common problem of a missed clinical examination because of an uncooperative or unresponsive patient, flash visual evoked potentials and electroretinograms should be used. These electrophysiologic examination techniques can provide evidence of intact, pathologic, or absent conductivity of the visual pathway when clinical assessment is not feasible. Visual evoked potentials and electroretinograms are thus essential diagnostic procedures not only for primary diagnosis but also for intraoperative evaluation. A decision for or against treatment of a visual pathway injury has to be made as fast as possible due to the enormous importance of the time elapsed with such injuries; this can be achieved additionally using multislice spiral computed tomography. The first-line conservative treatment of choice for such injuries is megadose methylprednisolone therapy. Surgery is used to decompress the orbital compartment by exposure of the intracanalicular part of the optic nerve in the case of optic canal compression. Modern craniomaxillofacial surgery requires detailed consideration of the diagnosis and treatment of traumatic visual pathway damage with the ultimate goal of preserving visual acuity. PMID:24436741

  20. Syntrophin isoforms play specific functional roles in the α1D-adrenergic receptor/DAPC signalosome

    PubMed Central

    Lyssand, John S.; Lee, Kyung-Soon; DeFino, Mia; Adams, Marvin E.; Hague, Chris

    2014-01-01

    α1D-Adrenergic receptors, key regulators of cardiovascular system function, are organized as a multi-protein complex in the plasma membrane. Using a Type-I PDZ-binding motif in their distal C-terminal domain, α1D-ARs associate with syntrophins and dystrophin-associated protein complex (DAPC) members utrophin, dystrobrevin and α-catulin. Three of the five syntrophin isoforms (α, β1 and β2) interact with α1D-ARs and our previous studies suggest multiple isoforms are required for proper α1D-AR function in vivo. This study determined the contribution of each specific syntrophin isoform to α1D-AR function. Radioligand binding experiments reveal α-syntrophin enhances α1D-AR binding site density, while phosphoinositol and ERK1/2 signaling assays indicate β2-syntrophin augments full and partial agonist efficacy for coupling to downstream signaling mechanisms. The results of this study provide clear evidence that the cytosolic components within the α1D-AR/DAPC signalosome significantly alter the pharmacological properties of α1-AR ligands in vitro. PMID:21846462

  1. beta-Arrestin mediates beta1-adrenergic receptor-epidermal growth factor receptor interaction and downstream signaling.

    PubMed

    Tilley, Douglas G; Kim, Il-Man; Patel, Priyesh A; Violin, Jonathan D; Rockman, Howard A

    2009-07-24

    beta1-Adrenergic receptor (beta1AR) stimulation confers cardioprotection via beta-arrestin-de pend ent transactivation of epidermal growth factor receptors (EGFRs), however, the precise mechanism for this salutary process is unknown. We tested the hypothesis that the beta1AR and EGFR form a complex that differentially directs intracellular signaling pathways. beta1AR stimulation and EGF ligand can each induce equivalent EGFR phosphorylation, internalization, and downstream activation of ERK1/2, but only EGF ligand causes translocation of activated ERK to the nucleus, whereas beta1AR-stimulated/EGFR-transactivated ERK is restricted to the cytoplasm. beta1AR and EGFR are shown to interact as a receptor complex both in cell culture and endogenously in human heart, an interaction that is selective and undergoes dynamic regulation by ligand stimulation. Although catecholamine stimulation mediates the retention of beta1AR-EGFR interaction throughout receptor internalization, direct EGF ligand stimulation initiates the internalization of EGFR alone. Continued interaction of beta1AR with EGFR following activation is dependent upon C-terminal tail GRK phosphorylation sites of the beta1AR and recruitment of beta-arrestin. These data reveal a new signaling paradigm in which beta-arrestin is required for the maintenance of a beta1AR-EGFR interaction that can direct cytosolic targeting of ERK in response to catecholamine stimulation.

  2. Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

    SciTech Connect

    Somogyi, G.T.; de Groat, W.C. )

    1990-10-01

    Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activation of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.

  3. [Beta]-Adrenergic Receptors in the Insular Cortex are Differentially Involved in Aversive vs. Incidental Context Memory Formation

    ERIC Educational Resources Information Center

    Miranda, Maria Isabel; Sabath, Elizabeth; Nunez-Jaramillo, Luis; Puron-Sierra, Liliana

    2011-01-01

    The goal of this research was to determine the effects of [beta]-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the [beta]-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition…

  4. Mechanisms of trigeminal nerve injuries.

    PubMed

    Ziccardi, V B; Assael, L A

    2001-09-01

    Injuries to the trigeminal nerve branches are a known and accepted risk in oral and maxillofacial surgery. It is prudent for the practitioner to explain the risks to patients as part of the informed consent process and to recognize and document the presence of nerve injury postoperatively. Patients should be referred to a surgeon experienced in microsurgical techniques in a timely fashion for evaluation and possible surgical intervention if an injury is not resolving.

  5. Somatostatinergic nerves in the cervical spinal cord of the monkey.

    PubMed

    Burnweit, C; Forssmann, W G

    1979-08-01

    Somatostatinergic nerves in the spinal cord of the monkey were investigated utilizing immunohistochemistry with various antibodies against synthetic somatostatin. In contrast to earlier investigations, it is shown that somatostatinergic nerve endings occur in most of the areas of the grey matter of the spinal cord. The somatostatinergic axons are, however, characteristically distributed in three main regions: (1) Densely-packed endings are seen in lamina II of the substantia gelatinosa, forming a crescent-shaped pattern in the columna dorsalis. Somatostatin immunoreactivity is also seen in lamina I and in the Lissauer tract. (2) A fine network of fibers is observed around the central canal; the endings are concentrated on special cell bodies. Some single perikarya are also stained in this region. (3) A loose network of single fibers is found ending on perikarya of the columna lateralis or ventralis. The perikarya of the nerve axons, with the exception of those terminating in the columna dorsalis, have as yet not been identified. In order to better understand the somatostatinergic system of the spinal cord, these newly-detected somatostatinergic nerves must be studied and their exact pathways analyzed.

  6. Effect of age on upregulation of the cardiac adrenergic beta receptors

    SciTech Connect

    Tumer, N.; Houck, W.T.; Roberts, J.

    1990-03-01

    Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors.

  7. Characterization of. cap alpha. /sub 2/-adrenergic receptors in rat cerebral cortex

    SciTech Connect

    Nasseri, A.

    1987-01-01

    The properties of /sup 3/H-RX 781094 binding sites and the receptors inhibiting norepinephrine (NE) release and cyclic AMP accumulation in rat cerebral cortex were compared. /sup 3/H-RX 781094, a new ..cap alpha../sub 2/-adrenergic receptor antagonist radioligand, labelled a homogeneous population of binding sites at 37/sup 0/C with the pharmacological specificity expected of ..cap alpha../sub 2/-adrenergic receptors. Gpp(NH)p and NaCl decreased the potencies of agonists at /sup 3/H-RX 781094 binding sites 3-22 fold. Antagonists blocked the inhibition of potassium-evoked tritium release from cortical slices preloaded with /sup 3/H-NE by exogenous NE with potencies similar to those observed in competition for specific /sup 3/H-RX 781094 binding sites. EEDQ, an irreversible ..cap alpha../sub 2/-adrenergic receptors and determine whether there was a receptor reserve for the inhibition of tritium release.

  8. Alpha-1 adrenergic receptors in the medial preoptic area are involved in the induction of sleep.

    PubMed

    Kumar, Velayudhan Mohan; Vetrivelan, Ramalingam; Mallick, Hruda Nanda

    2006-08-01

    This paper reviews the recent studies that led to the conclusion that the noradrenergic neurons projecting to the medial preoptic area (mPOA) are hypnogenic and that they mediate this action through alpha(1) adrenergic receptors. Microinjection of noradrenaline (NA) into the mPOA induced arousal. Studies using alpha(2) adrenergic drugs showed that the arousal induced by intrapreoptic injection of NA was due to its action on presynaptic alpha(2) adrenergic receptors. A combination of lesion and chemical stimulation techniques demonstrated that when NA acted on the postsynaptic alpha(1 )receptors in the mPOA, it induced sleep. Intrapreoptic injection of alpha(1) agonist, methoxamine could induce sleep, when the hypothermia, which was simultaneously produced, was behaviorally compensated for by the animal. Increased arousal produced by the destruction of noradrenergic fibers in the mPOA further confirmed the hypnogenic role of these fibers.

  9. Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists.

    PubMed

    Weichert, Dietmar; Stanek, Markus; Hübner, Harald; Gmeiner, Peter

    2016-06-15

    Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describe the design, synthesis and biological investigation of a defined set of compounds leading to the identification of the benzoxazinone (R)-3, which shows agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D2 receptor. This directed approach yielded molecular probes with tuned dual activity. The congener desOH-3 devoid of the benzylic hydroxyl function was shown to be a β2 adrenergic antagonist/D2 receptor agonist with Ki values in the low nanomolar range. The compounds may serve as a promising starting point for the investigation and treatment of neurological disorders. PMID:27132867

  10. [Peripheral Nerve Injuries in Sports].

    PubMed

    Tettenborn, B; Mehnert, S; Reuter, I

    2016-09-01

    Peripheral nerve injuries due to sports are relatively rare but the exact incidence is not known due to a lack of epidemiological studies. Particular sports activities tend to cause certain peripheral nerve injuries including direct acute compression or stretching, repetitive compression and stretching over time, or another mechanism such as ischemia or laceration. These nerve lesions may be severe and delay or preclude the athlete's return to sports, especially in cases with delayed diagnosis. Repetitive and vigorous use or overuse makes the athlete vulnerable to disorders of the peripheral nerves, and sports equipment may cause compression of the nerves. Depending on etiology, the treatment is primarily conservative and includes physiotherapy, modification of movements and sports equipment, shoe inserts, splinting, antiphlogistic drugs, sometimes local administration of glucocorticoids or, lately, the use of extracorporeal shock waves. Most often, cessation of the offending physical activity is necessary. Surgery is only indicated in the rare cases of direct traumatic nerve injury or when symptoms are refractory to conservative therapy. Prognosis mainly depends on the etiology and the available options of modifying measures.This article is based on the publications "Reuter I, Mehnert S. Engpasssyndrome peripherer Nerven bei Sportlern". Akt Neurol 2012;39:292-308 and Sportverl Sportschad 2013;27:130-146. PMID:27607069

  11. Noninvasive imaging of peripheral nerves.

    PubMed

    Rangavajla, Gautam; Mokarram, Nassir; Masoodzadehgan, Nazanin; Pai, S Balakrishna; Bellamkonda, Ravi V

    2014-01-01

    Recent developments in the field of peripheral nerve imaging extend the capabilities of imaging modalities to assist in the diagnosis and treatment of patients with peripheral nerve maladies. Methods such as magnetic resonance imaging (MRI) and its derivative diffusion tensor imaging (DTI), ultrasound (US) and positron emission tomography (PET) are capable of assessing nerve structure and function following injury and relating the state of the nerve to electrophysiological and histological analysis. Of the imaging methods surveyed here, each offered unique and interesting advantages related to the field. MRI offered the opportunity to visualize immune activity on the injured nerve throughout the course of the regeneration process, and DTI offered numerical characterization of the injury and the ability to develop statistical bases for diagnosing injury. US extends imaging to the treatment phase by enabling more precise analgesic applications following surgery, and PET represents a novel method of assessing nerve injury through analysis of relative metabolism rates in injured and healthy tissue. Exciting new possibilities to enhance and extend the abilities of imaging methods are also discussed, including innovative contrast agents, some of which enable multimodal imaging approaches and present opportunities for treatment application. PMID:25766202

  12. Cloning and expression of a rat brain. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H. )

    1991-02-01

    The authors isolated a cDNA clone (RB{alpha}{sub 2B}) and its homologous gene (GR{alpha}{sub 2B}) encoding an {alpha}{sub 2B}-adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor ({alpha}{sub 2}-C4) and divergent from the rat kidney nonglycosylated {alpha}{sub 2B} subtype (RNG{alpha}{sub 2}). Transient expression of RB{alpha}{sub 2B} in COS-7 cells resulted in high-affinity saturable binding for ({sup 3}H)rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine {gt} yohimbine {gt} prazosin {gt} oxymetazoline, with a prazosin-to-oxymetazoline K{sub i} ratio of 0.34. This profile is characteristic of the {alpha}{sub 2B}-adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GR{alpha}{sub 2B} may be transcriptionally active. These findings show that rat brain expresses an {alpha}{sub 2B}-adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated {alpha}{sub 2B} subtype. Thus the rat expresses at least two divergent {alpha}{sub 2B}-adrenergic receptors.

  13. Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

    PubMed

    Wofford, M R; Anderson, D C; Brown, C A; Jones, D W; Miller, M E; Hall, J E

    2001-07-01

    The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

  14. Beta(2)-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation.

    PubMed

    Aránguiz-Urroz, Pablo; Canales, Jimena; Copaja, Miguel; Troncoso, Rodrigo; Vicencio, Jose Miguel; Carrillo, Constanza; Lara, Hernán; Lavandero, Sergio; Díaz-Araya, Guillermo

    2011-01-01

    Autophagy is a physiological degradative process key to cell survival during nutrient deprivation, cell differentiation and development. It plays a major role in the turnover of damaged macromolecules and organelles, and it has been involved in the pathogenesis of different cardiovascular diseases. Activation of the adrenergic system is commonly associated with cardiac fibrosis and remodeling, and cardiac fibroblasts are key players in these processes. Whether adrenergic stimulation modulates cardiac fibroblast autophagy remains unexplored. In the present study, we aimed at this question and evaluated the effects of b(2)-adrenergic stimulation upon autophagy. Cultured adult rat cardiac fibroblasts were treated with agonists or antagonists of beta-adrenergic receptors (b-AR), and autophagy was assessed by electron microscopy, GFP-LC3 subcellular distribution, and immunowesternblot of endogenous LC3. The predominant expression of b(2)-ARs was determined and characterized by radioligand binding assays using [(3)H]dihydroalprenolol. Both, isoproterenol and norepinephrine (non-selective b-AR agonists), as well as salbutamol (selective b(2)-AR agonist) increased autophagic flux, and these effects were blocked by propanolol (b-AR antagonist), ICI-118,551 (selective b(2)-AR antagonist), 3-methyladenine but not by atenolol (selective b(1)-AR antagonist). The increase in autophagy was correlated with an enhanced degradation of collagen, and this effect was abrogated by the inhibition of autophagic flux. Overall, our data suggest that b(2)-adrenergic stimulation triggers autophagy in cardiac fibroblasts, and that this response could contribute to reduce the deleterious effects of high adrenergic stimulation upon cardiac fibrosis. PMID:20637865

  15. Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat brain regions.

    PubMed

    Hadjiivanova, Ch I; Petkov, V V

    2002-08-01

    The effect of oral administration of Ginkgo biloba extract at a dose of 90 mg/kg for 7 consecutive days on rat brain beta-adrenergic receptors in the frontal cortex, hippocampus, striatum and hypothalamus was studied. Ginkgo biloba treatment induced a significant decrease in the density (B(max)) of beta-adrenoreceptors in the frontal cortex and hippocampus. It has been suggested that modulation of the beta-adrenergic system is implicated in the favourable effects of Ginkgo biloba extracts on learning and memory.

  16. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    PubMed

    Ramseyer, Vanesa D; Granneman, James G

    2016-01-01

    The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct β-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes.

  17. Beta 2-adrenergic agonist as adjunct therapy to levodopa in Parkinson's disease.

    PubMed

    Alexander, G M; Schwartzman, R J; Nukes, T A; Grothusen, J R; Hooker, M D

    1994-08-01

    We studied the effect of the beta 2-adrenergic agonist albuterol on Parkinson's disease (PD) patients receiving chronic levodopa treatment. The albuterol-treated patients demonstrated reduced parkinsonian symptoms and an increased ability to tap their index finger between two points 20 cm apart, and were able to perform a "walk test" in 70% of their control time. Three patients currently on chronic albuterol therapy still show amelioration of their parkinsonian symptoms, and two have reduced their daily levodopa dose. This study suggests that beta 2-adrenergic agonists as adjunct therapy to levodopa may be beneficial in PD.

  18. Inhaled adrenergics and anticholinergics in obstructive lung disease: do they enhance mucociliary clearance?

    PubMed

    Restrepo, Ruben D

    2007-09-01

    Pulmonary mucociliary clearance is an essential defense mechanism against bacteria and particulate matter. Mucociliary dysfunction is an important feature of obstructive lung diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, and bronchiectasis. This dysfunction in airway clearance is associated with accelerated loss of lung function in patients with obstructive lung disease. The involvement of the cholinergic and adrenergic neural pathways in the pathophysiology of mucus hypersecretion suggests the potential therapeutic role of bronchodilators as mucoactive agents. Although anticholinergics and adrenergic agonist bronchodilators have been routinely used, alone or in combination, to enhance mucociliary clearance in patients with obstructive lung disease, the existing evidence does not consistently show clinical effectiveness.

  19. Beta-adrenergic stimulation of phagocytosis in the unicellular eukaryote Paramecium aurelia.

    PubMed

    Wyroba, E

    1989-08-01

    Bete-adrenergic agonists isoproterenol and norepinephrine enhanced phagocytosis in Paramecium. Stimulation was stereospecific, dose-dependent and inhibited by the beta-agonists propranolol and alprenolol. Phorbol ester and forskolin potentiated the stimulatory effect of catecholamines on Paramecium phagocytosis. The dansyl analogue of propranolol (DAPN) was used for fluorescent visualization of the beta-adrenergic receptor sites in Paramecium which have been found to be localized at the cell membrane and within the membrane of the nascent digestive vacuoles. The appearance of the characteristic fluorescent pattern has been blocked by 1-propranolol.

  20. β-Adrenergic response is counteracted by extremely-low-frequency pulsed electromagnetic fields in beating cardiomyocytes.

    PubMed

    Cornacchione, Marisa; Pellegrini, Manuela; Fassina, Lorenzo; Mognaschi, Maria Evelina; Di Siena, Sara; Gimmelli, Roberto; Ambrosino, Paolo; Soldovieri, Maria Virginia; Taglialatela, Maurizio; Gianfrilli, Daniele; Isidori, Andrea M; Lenzi, Andrea; Naro, Fabio

    2016-09-01

    Proper β-adrenergic signaling is indispensable for modulating heart frequency. Studies on extremely-low-frequency pulsed electromagnetic field (ELF-PEMF) effects in the heart beat function are contradictory and no definitive conclusions were obtained so far. To investigate the interplay between ELF-PEMF exposure and β-adrenergic signaling, cultures of primary murine neonatal cardiomyocytes and of sinoatrial node were exposed to ELF-PEMF and short and long-term effects were evaluated. The ELF-PEMF generated a variable magnetic induction field of 0-6mT at a frequency of 75Hz. Exposure to 3mT ELF-PEMF induced a decrease of contraction rate, Ca(2+) transients, contraction force, and energy consumption both under basal conditions and after β-adrenergic stimulation in neonatal cardiomyocytes. ELF-PEMF exposure inhibited β-adrenergic response in sinoatrial node (SAN) region. ELF-PEMF specifically modulated β2 adrenergic receptor response and the exposure did not modify the increase of contraction rate after adenylate cyclase stimulation by forskolin. In HEK293T cells transfected with β1 or β2 adrenergic receptors, ELF-PEMF exposure induced a rapid and selective internalization of β2 adrenergic receptor. The β-adrenergic signaling, was reduced trough Gi protein by ELF-PEMF exposure since the phosphorylation level of phospholamban and the PI3K pathway were impaired after isoproterenol stimulation in neonatal cardiomyocytes. Long term effects of ELF-PEMF exposure were assessed in cultures of isolated cardiomyocytes. ELF-PEMF counteracts cell size increase, the generation of binucleated of cardiomyocytes and prevents the up-regulation of hypertrophic markers after β-adrenergic stimulation, indicating an inhibition of cell growth and maturation. These data show that short and long term exposure to ELF-PEMF induces a reduction of cardiac β-adrenergic response at molecular, functional and adaptative levels.

  1. Postsynaptic alpha-2 adrenergic receptors are critical for the antidepressant-like effects of desipramine on behavior.

    PubMed

    Zhang, Han-Ting; Whisler, Lisa R; Huang, Ying; Xiang, Yang; O'Donnell, James M

    2009-03-01

    The antidepressant desipramine inhibits the reuptake of norepinephrine (NE), leading to activation of both pre- and postsynaptic adrenergic receptors, including alpha-1, alpha-2, beta-1, and beta-2 subtypes. However, it is not clear which adrenergic receptors are involved in mediating its antidepressant effects. Treatment of mice with desipramine (20 mg/kg, i.p.) produced an antidepressant-like effect, as evidenced by decreased immobility in the forced-swim test; this was antagonized by pretreatment with the alpha-2 adrenergic antagonist idazoxan (0.1-2.5 mg/kg, i.p.). Similarly, idazoxan, administered peripherally (0.5-2.5 mg/kg, i.p.) or centrally (1-10 microg, i.c.v.), antagonized the antidepressant-like effect of desipramine in rats responding under a differential-reinforcement-of-low-rate (DRL) 72-s schedule, ie, decreased response rate and increased reinforcement rate. By contrast, pretreatment with the beta-adrenergic antagonists propranolol and CGP-12177 or the alpha-1 adrenergic antagonist prazosin did not alter the antidepressant-like effect of desipramine on DRL behavior. The lack of involvement of beta-adrenergic receptors in mediating the behavioral effects of desipramine was confirmed using knockout lines. In the forced-swim test, the desipramine-induced decrease in immobility was not altered in mice deficient in beta-1, beta-2, or both beta-1 and beta-2 adrenergic receptors. In addition, desipramine (3-30 mg/kg) produced an antidepressant-like effect on behavior under a DRL 36-s schedule in mice deficient in both beta-1 and beta-2 adrenergic receptors. As antagonism of presynaptic alpha-2 adrenergic receptors facilitates NE release, which potentiates the effects of desipramine, the present results suggest that postsynaptic alpha-2 adrenergic receptors play an important role in its antidepressant effects.

  2. β-Adrenergic response is counteracted by extremely-low-frequency pulsed electromagnetic fields in beating cardiomyocytes.

    PubMed

    Cornacchione, Marisa; Pellegrini, Manuela; Fassina, Lorenzo; Mognaschi, Maria Evelina; Di Siena, Sara; Gimmelli, Roberto; Ambrosino, Paolo; Soldovieri, Maria Virginia; Taglialatela, Maurizio; Gianfrilli, Daniele; Isidori, Andrea M; Lenzi, Andrea; Naro, Fabio

    2016-09-01

    Proper β-adrenergic signaling is indispensable for modulating heart frequency. Studies on extremely-low-frequency pulsed electromagnetic field (ELF-PEMF) effects in the heart beat function are contradictory and no definitive conclusions were obtained so far. To investigate the interplay between ELF-PEMF exposure and β-adrenergic signaling, cultures of primary murine neonatal cardiomyocytes and of sinoatrial node were exposed to ELF-PEMF and short and long-term effects were evaluated. The ELF-PEMF generated a variable magnetic induction field of 0-6mT at a frequency of 75Hz. Exposure to 3mT ELF-PEMF induced a decrease of contraction rate, Ca(2+) transients, contraction force, and energy consumption both under basal conditions and after β-adrenergic stimulation in neonatal cardiomyocytes. ELF-PEMF exposure inhibited β-adrenergic response in sinoatrial node (SAN) region. ELF-PEMF specifically modulated β2 adrenergic receptor response and the exposure did not modify the increase of contraction rate after adenylate cyclase stimulation by forskolin. In HEK293T cells transfected with β1 or β2 adrenergic receptors, ELF-PEMF exposure induced a rapid and selective internalization of β2 adrenergic receptor. The β-adrenergic signaling, was reduced trough Gi protein by ELF-PEMF exposure since the phosphorylation level of phospholamban and the PI3K pathway were impaired after isoproterenol stimulation in neonatal cardiomyocytes. Long term effects of ELF-PEMF exposure were assessed in cultures of isolated cardiomyocytes. ELF-PEMF counteracts cell size increase, the generation of binucleated of cardiomyocytes and prevents the up-regulation of hypertrophic markers after β-adrenergic stimulation, indicating an inhibition of cell growth and maturation. These data show that short and long term exposure to ELF-PEMF induces a reduction of cardiac β-adrenergic response at molecular, functional and adaptative levels. PMID:27418252

  3. Regulation of β-adrenergic control of heart rate by GTP-cyclohydrolase 1 (GCH1) and tetrahydrobiopterin

    PubMed Central

    Adlam, David; Herring, Neil; Douglas, Gillian; De Bono, Joseph P.; Li, Dan; Danson, Edward J.; Tatham, Amy; Lu, Cheih-Ju; Jennings, Katie A.; Cragg, Stephanie J.; Casadei, Barbara; Paterson, David J.; Channon, Keith M.

    2012-01-01

    Aims Clinical markers of cardiac autonomic function, such as heart rate and response to exercise, are important predictors of cardiovascular risk. Tetrahydrobiopterin (BH4) is a required cofactor for enzymes with roles in cardiac autonomic function, including tyrosine hydroxylase and nitric oxide synthase. Synthesis of BH4 is regulated by GTP cyclohydrolase I (GTPCH), encoded by GCH1. Recent clinical studies report associations between GCH1 variants and increased heart rate, but the mechanistic importance of GCH1 and BH4 in autonomic function remains unclear. We investigate the effect of BH4 deficiency on the autonomic regulation of heart rate in the hph-1 mouse model of BH4 deficiency. Methods and results In the hph-1 mouse, reduced cardiac GCH1 expression, GTPCH enzymatic activity, and BH4 were associated with increased resting heart rate; blood pressure was not different. Exercise training decreased resting heart rate, but hph-1 mice retained a relative tachycardia. Vagal nerve stimulation in vitro induced bradycardia equally in hph-1 and wild-type mice both before and after exercise training. Direct atrial responses to carbamylcholine were equal. In contrast, propranolol treatment normalized the resting tachycardia in vivo. Stellate ganglion stimulation and isoproterenol but not forskolin application in vitro induced a greater tachycardic response in hph-1 mice. β1-adrenoceptor protein was increased as was the cAMP response to isoproterenol stimulation. Conclusion Reduced GCH1 expression and BH4 deficiency cause tachycardia through enhanced β-adrenergic sensitivity, with no effect on vagal function. GCH1 expression and BH4 are novel determinants of cardiac autonomic regulation that may have important roles in cardiovascular pathophysiology. PMID:22241166

  4. Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb.

    PubMed

    Heinonen, Ilkka; Wendelin-Saarenhovi, Maria; Kaskinoro, Kimmo; Knuuti, Juhani; Scheinin, Mika; Kalliokoski, Kari K

    2013-07-15

    The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ~40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min(-1)·100 g(-1) in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min(-1)·100 g(-1)) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min(-1)·100 g(-1)). During exercise, NE reduced exercising muscle BF by ~16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT (P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

  5. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    PubMed

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  6. How the optic nerve allocates space, energy capacity, and information.

    PubMed

    Perge, János A; Koch, Kristin; Miller, Robert; Sterling, Peter; Balasubramanian, Vijay

    2009-06-17

    Fiber tracts should use space and energy efficiently, because both resources constrain neural computation. We found for a myelinated tract (optic nerve) that astrocytes use nearly 30% of the space and >70% of the mitochondria, establishing the significance of astrocytes for the brain's space and energy budgets. Axons are mostly thin with a skewed distribution peaking at 0.7 microm, near the lower limit set by channel noise. This distribution is matched closely by the distribution of mean firing rates measured under naturalistic conditions, suggesting that firing rate increases proportionally with axon diameter. In axons thicker than 0.7 microm, mitochondria occupy a constant fraction of axonal volume--thus, mitochondrial volumes rise as the diameter squared. These results imply a law of diminishing returns: twice the information rate requires more than twice the space and energy capacity. We conclude that the optic nerve conserves space and energy by sending most information at low rates over fine axons with small terminal arbors and sending some information at higher rates over thicker axons with larger terminal arbors but only where more bits per second are needed for a specific purpose. Thicker axons seem to be needed, not for their greater conduction velocity (nor other intrinsic electrophysiological purpose), but instead to support larger terminal arbors and more active zones that transfer information synaptically at higher rates. PMID:19535603

  7. Occurrence, distribution and origin of peptide-containing nerves of guinea-pig and rat male genitalia and the effects of denervation on sperm characteristics.

    PubMed Central

    Carvalho, T L; Hodson, N P; Blank, M A; Watson, P F; Mulderry, P K; Bishop, A E; Gu, J; Bloom, S R; Polak, J M

    1986-01-01

    A systematic immunohistochemical and radio-immunological survey of the occurrence, distribution and origin of the peptidergic nerve supply in guinea-pig and rat male genitalia is presented. Neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P and CGRP were detected in the genital organs of both species. The densities and distribution patterns of the peptidergic nerves were compared with those of the adrenergic nerves, as revealed by antibodies raised against dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH), and the general neuronal component, as revealed by antibodies raised against neurofilament proteins (NF). Bilateral transection of the hypogastric nerves, in the guinea-pig, resulted in a decrease of substance P-containing nerves in the vas deferens and of NPY-, PHI- and VIP-containing nerves in the seminal vesicle. Unilateral disconnection of the pelvic nerves caused a decrease of VIP, PHI, substance P and CGRP nerve supply in the ipsilateral vas deferens and cauda epididymidis in the guinea-pig. A marked reduction of noradrenergic and NPY-containing nerves was observed in the vas deferens and sexual accessory glands of rats, chemically sympathectomised by chronic injection of low doses of guanethidine. Conversely, increase of substance P and CGRP immunoreactivities were observed, particularly in the vas deferens. After guanethidine, the cauda epididymidis and vas deferens were distended with spermatozoa, suggesting paralysis of the ducts. Spermatozoa had a decreased percentage of attached cytoplasmic droplets, indicating prolonged retention in the ducts. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3693101

  8. Disruption of Lateral Olivocochlear Neurons With a Dopaminergic Neurotoxin Depresses Spontaneous Auditory Nerve Activity

    PubMed Central

    Le Prell, Colleen G.; Dolan, David F.; Hughes, Larry F.; Altschuler, Richard A.; Shore, Susan E.; Bledsoe, Sanford C.

    2015-01-01

    Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. PMID:25175420

  9. Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.

    PubMed

    Le Prell, Colleen G; Dolan, David F; Hughes, Larry F; Altschuler, Richard A; Shore, Susan E; Bledsoe, Sanford C

    2014-10-17

    Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs. PMID:25175420

  10. In-continuity neuroma of the median nerve at the elbow.

    PubMed

    Alessandrino, Francesco; Pagani, C; Draghi, F

    2014-09-01

    Neuromas are a hyperplastic disorganised proliferation of cells that represent an attempt at nerve regeneration after trauma. They can be classified into terminal and in-continuity neuromas; the latter are observed when the nerve stumps are both connected. We present here the case of a 46-year-old male who sustained a deep cut at the volar aspect of the right elbow while repairing a glass. The injury caused partial transection of the median nerve, which was initially unrecognised. After several months, the patient presented pain at the volar aspect of the elbow, worsening with manual compression at the site of previous injury. Ultrasound showed an in-continuity neuroma with a hypoechoic and enlarged median nerve at the site of the sutured wound. The case report shows that ultrasound may be helpful in confirming the clinical diagnosis of neuroma and that it is useful to evaluate the percentage of the area affected by the lesion.

  11. Comparative pharmacology of adrenergic alpha(2C) receptors coupled to Ca(2+) signaling through different Galpha proteins.

    PubMed

    Kurko, Dalma; Bekes, Zsófia; Gere, Anikó; Baki, Andrea; Boros, András; Kolok, Sándor; Bugovics, Gyula; Nagy, József; Szombathelyi, Zsolt; Ignácz-Szendrei, Györgyi

    2009-12-01

    Adrenergic alpha(1), alpha(2) and beta receptors are members of the G-protein-coupled receptor families (GPCRs) mediating physiological responses to adrenaline (epinephrine) and noradrenaline (norepinephrine). Since GPCRs are major targets for potential therapeutic agents, development of robust, reliable and cost effective functional screening methods for these receptors is in the focus of pharmacological research. For this reason, the aim of the present study was to develop an intracellular calcium assay for investigating the pharmacology of the alpha(2C) type of adrenergic receptors (alpha(2C)-AR). Although activation of alpha(2C)-AR is not linked to calcium mobilization, co-expression of these receptors with the chimeric Galpha(qi5) protein, containing the five carboxyl-terminal amino acids from G(i), or promiscuosus Galpha(16) protein can divert receptor signaling to the G(q) pathway generating Ca(2+) release from intracellular stores. In order to assess the functional potency of alpha(2)-AR agonists and antagonists, we established a fluorometric Ca(2+) assay using cell lines stably and constitutively co-expressing alpha(2C)-AR and Galpha(qi5) or Galpha(16) proteins (Galpha(qi5)/alpha(2C) and Galpha(16)/alpha(2C)). As part of the pharmacological characterization, we measured the changes in cytoplasmic Ca(2+) levels due to activation of the chimeric Galpha(qi5) or Galpha(16) coupled recombinant alpha(2C) receptors as a function of increasing concentration of several agonists (noradrenaline, brimonidine, oxymetazoline, clonidine, moxonidine) and antagonists (MK912, yohimbine). The binding affinities of alpha(2)-AR agonist and antagonists and the inhibition of the forskolin-stimulated cAMP accumulation in alpha(2C)-AR expressing cells were also measured. These results confirmed that the Galpha(qi5)/alpha(2C) and Galpha(16)/alpha(2C) recombinant systems can be useful for modelling the native G(i)-coupled system. Our results indicate that a plate-reader based

  12. Electrophysiological characterization of peptidergic neurosecretory terminals.

    PubMed

    Cooke, I M

    1985-09-01

    Electrical activity recorded intracellularly from peptidergic neurosecretory terminal dilatations in the sinus gland of crabs (principally Cardisoma guanhumi and C. carnifex) is described. Recordings were made from the neurohaemal organ in situ on the neural tissue of the isolated eyestalk and from isolated sinus gland-sinus gland nerve preparations. Verification that electrodes penetrated terminals was obtained by dye marking. Resting potentials ranged between -30 and -80mV. Overshooting action potentials of long duration (5-20 ms at 1/2 amplitude) relative to those of non-secretory axons (less than 2ms) were recorded in approximately 70% of stable penetrations. Action potentials occurred spontaneously at slow (less than 0.2s-1) rates in 75% of penetrations. Sequential intra- and extracellular recordings with the same microelectrode, on the same terminal, indicate impulse generation by the terminal itself. Extracellular stimulation of the axon tract evokes an all-or-none action potential at distinct threshold and latency. At rates of stimulation exceeding 5s-1, discrete fluctuations in the form of responses occur. Similar waveforms occur spontaneously and can be evoked by passing current through the electrode. They are interpreted to be electrotonically recorded activity of other parts of a complex axonal terminal arborization. Some, but not all, terminals exhibit impulse broadening (up to three-fold at 1/2 amplitude) during repetitive firing exceeding 1s-1. The same terminals show reduced impulse duration with hyperpolarization and broadened impulses with imposed depolarization. The changes are due to altered repolarization rates. Terminals sustain steady impulse firing at rates (up to 5s-1) linearly related to the imposed depolarizing current. Regenerative potentials, though of reduced rate of rise and amplitude, can be evoked by depolarizing current passed through the electrode during perfusion with salines having 1/2 normal [Na+], or containing tetrodotoxin

  13. Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

    PubMed

    Sieber, C C; Sumanovski, L T; Moll-Kaufmann, C; Stalder, G A

    1997-11-01

    Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition PMID:9395785

  14. Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

    PubMed

    Sieber, C C; Sumanovski, L T; Moll-Kaufmann, C; Stalder, G A

    1997-11-01

    Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition

  15. The Alpha-1A Adrenergic Receptor in the Rabbit Heart.

    PubMed

    Thomas, R Croft; Cowley, Patrick M; Singh, Abhishek; Myagmar, Bat-Erdene; Swigart, Philip M; Baker, Anthony J; Simpson, Paul C

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  16. The Alpha-1A Adrenergic Receptor in the Rabbit Heart

    PubMed Central

    Myagmar, Bat-Erdene; Swigart, Philip M.; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  17. Beta-Adrenergic Receptor Expression in Muscle Cells

    NASA Technical Reports Server (NTRS)

    Young, Ronald B.; Bridge, K.; Vaughn, J. R.

    1999-01-01

    beta-adrenergic receptor (bAR) agonists presumably exert their physiological action on skeletal muscle cells through the bAR. Since the signal generated by the bAR is cyclic AMP (cAMP), experiments were initiated in primary chicken muscle cell cultures to determine if artificial elevation of intracellular cAMP by treatment with forskolin would alter the population of bAR expressed on the surface of muscle cells. Chicken skeletal muscle cells after 7 days in culture were employed for the experiments because muscle cells have attained a steady state with respect to muscle protein metabolism at this stage. Cells were treated with 0-10 uM forskolin for a total of three days. At the end of the 1, 2, and 3 day treatment intervals, the concentration of cAMP and the bAR population were measured. Receptor population was measured in intact muscle cell cultures as the difference between total binding of [H-3]CGP-12177 and non-specific binding of [H-3]CGP-12177 in the presence of 1 uM propranolol. Intracellular cAMP concentration was measured by radioimmunoassay. The concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. Increasing concentrations of forskolin also led to an increase in (beta)AR population, with a maximum increase of approximately 50% at 10 uM. This increase in (beta)AR population was apparent after only 1 day of treatment, and the pattern of increase was maintained for all 3 days of the treatment period. Thus, increasing the intracellular concentration of cAMP leads to up-regulation of (beta)AR population. Clenbuterol and isoproterenol gave similar effects on bAR population. The effect of forskolin on the quantity and apparent synthesis rate of the heavy chain of myosin (mhc) were also investigated. A maximum increase of 50% in the quantity of mhc was observed at 0.2 UM forskolin, but higher concentrations of forskolin reduced the quantity of mhc back to control levels.

  18. Fine morphological changes in the penicillate nerve endings of human hairy skin during prolonged itching.

    PubMed

    Cauna, N

    1977-05-01

    Morphological changes in cutaneous nerve endings were investigated electron microscopically in patients suffering from certain kinds of urticaria with associated itching and in normal skin in which wheals and local itching were induced either by application of nettle hairs or by intracutaneous injections of a timothy pollen extract. Skin samples were obtained with a high speed dermal punch without anesthesia from the wheal areas. It was found that some subepidermal free nerve endings derived from non-myelinated nerve fibers (penicillate endings) showed accumulations of extra-cytoplasmic glycogen which was localized in the distended spaces between the axolemma, the Schwann cell membrane and the nerve basement membrane. In some cases, the glycogen was found to be so abundant that it occupied most of the cross sectional area of the ending. No morphological changes were observed in the pappilary endings, in nerve endings of the hairs or in the autonomic terminals. The conducting segments of all cutaneous nerve fibers showed normal morphology. The unusual morphological changes that occur in some penicillate nerve endings during the wheal development indicate that these endings are involved in the skin reaction and therefore they may be the specific end organs that are associated with itch, at least in urticaria. PMID:869227

  19. Novel use of biodegradable casein conduits for guided peripheral nerve regeneration.

    PubMed

    Hsiang, Shih-Wei; Tsai, Chin-Chuan; Tsai, Fuu-Jen; Ho, Tin-Yun; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2011-11-01

    Recent advances in nerve repair technology have focused on finding more biocompatible, non-toxic materials to imitate natural peripheral nerve components. In this study, casein protein cross-linked with naturally occurring genipin (genipin-cross-linked casein (GCC)) was used for the first time to make a biodegradable conduit for peripheral nerve repair. The GCC conduit was dark blue in appearance with a concentric and round lumen. Water uptake, contact angle and mechanical tests indicated that the conduit had a high stability in water and did not collapse and cramped with a sufficiently high level of mechanical properties. Cytotoxic testing and terminal deoxynucleotidyl transferase dUTP nick-end labelling assay showed that the GCC was non-toxic and non-apoptotic, which could maintain the survival and outgrowth of Schwann cells. Non-invasive real-time nuclear factor-κB bioluminescence imaging accompanied by histochemical assessment showed that the GCC was highly biocompatible after subcutaneous implantation in transgenic mice. Effectiveness of the GCC conduit as a guidance channel was examined as it was used to repair a 10 mm gap in the rat sciatic nerve. Electrophysiology, labelling of calcitonin gene-related peptide in the lumbar spinal cord, and histology analysis all showed a rapid morphological and functional recovery for the disrupted nerves. Therefore, we conclude that the GCC can offer great nerve regeneration characteristics and can be a promising material for the successful repair of peripheral nerve defects.

  20. Cytochemical demonstration of cholinergic, serotoninergic and peptidergic nerve elements in Gorgoderina vitelliloba (Trematoda: Digenea).

    PubMed

    McKay, D M; Halton, D W; Johnston, C F; Fairweather, I; Shaw, C

    1991-02-01

    Standard enzyme cytochemical and indirect immunocytochemical techniques have been used in conjunction with light and confocal scanning laser microscopy (CSLM) to visualize cholinergic, serotoninergic and peptidergic nerve elements in whole-mount preparations of the amphibian urinary-bladder fluke, Gorgoderina vitelliloba. Cholinesterase (ChE) activity was localized in paired anterior ganglia, a connecting dorsal commissure and in the origins of the ventral nerve cords. Cholinergic ganglia were also evident in shelled embryos in the uterus. Serotonin-immunoreactivity (IR) was more extensive than ChE activity and was identified in both the central and peripheral nervous systems. Serotoninergic nerve fibres were associated with the somatic musculature and female reproductive ducts. Antisera to nine mammalian peptides and one invertebrate (FMRFamide) peptide have been used to investigate the peptidergic nervous system in the parasite. Immunoreactivity was obtained to five peptides, namely pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP) and FMRFamide. Peptidergic nerve fibres were found to be more abundant than demonstrable cholinergic or serotoninergic nerve fibres. NPY-IR was identified only in the main components of the central nervous system. However, PP- and PYY-IR occurred in the anterior ganglia, dorsal commissure, main nerve cords and in numerous small varicose fibres that ramified throughout the worm. Additionally, PP-immunoreactive nerve fibres were found to innervate the musculature of the female reproductive tracts. Six sites of IR were found in the acetabulum, using antisera directed towards the C-terminal end of PP and PYY, and these matched with the distribution of six non-ciliated rosette-like papillae observed by scanning electron microscopy. SP- and FMRFamide-IR were identified in the CNS, and FMRFamide-immunopositive nerve fibres were also evident in association with the gonopore cirrus region and with the

  1. Terminal Air Flow Planning

    NASA Technical Reports Server (NTRS)

    Denery, Dallas G.; Erzberger, Heinz; Edwards, Thomas A. (Technical Monitor)

    1998-01-01

    The Center TRACON Automation System (CTAS) will be the basis for air traffic planning and control in the terminal area. The system accepts arriving traffic within an extended terminal area and optimizes the flow based on current traffic and airport conditions. The operational use of CTAS will be presented together with results from current operations.

  2. Superconducting Cable Termination

    DOEpatents

    Sinha, Uday K.; Tolbert, Jerry

    2005-08-30

    Disclosed is a termination that connects high temperature superconducting (HTS) cable immersed in pressurized liquid nitrogen to high voltage and neutral (shield) external bushings at ambient temperature and pressure. The termination consists of a splice between the HTS power (inner) and shield (outer) conductors and concentric copper pipes which are the conductors in the termination. There is also a transition from the dielectric tape insulator used in the HTS cable to the insulators used between and around the copper pipe conductors in the termination. At the warm end of the termination the copper pipes are connected via copper braided straps to the conventional warm external bushings which have low thermal stresses. This termination allows for a natural temperature gradient in the copper pipe conductors inside the termination which enables the controlled flashing of the pressurized liquid coolant (nitrogen) to the gaseous state. Thus the entire termination is near the coolant supply pressure and the high voltage and shield cold bushings, a highly stressed component used in most HTS cables, are eliminated. A sliding seal allows for cable contraction as it is cooled from room temperature to ˜72-82 K. Seals, static vacuum, and multi-layer superinsulation minimize radial heat leak to the environment.

  3. Cranial Nerves IX, X, XI, and XII

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    This article concludes the series on cranial nerves, with review of the final four (IX–XII). To summarize briefly, the most important and common syndrome caused by a disorder of the glossopharyngeal nerve (craniel nerve IX) is glossopharyngeal neuralgia. Also, swallowing function occasionally is compromised in a rare but disabling form of tardive dyskinesia called tardive dystonia, because the upper motor portion of the glossopharyngel nerve projects to the basal ganglia and can be affected by lesions in the basal ganglia. Vagus nerve funtion (craniel nerve X) can be compromised in schizophrenia, bulimia, obesity, and major depression. A cervical lesion to the nerve roots of the spinal accessory nerve (craniel nerve XI) can cause a cervical dystonia, which sometimes is misdiagnosed as a dyskinesia related to neuroleptic use. Finally, unilateral hypoglossal (craniel nerve XII) nerve palsy is one of the most common mononeuropathies caused by brain metastases. Supranuclear lesions of cranial nerve XII are involved in pseudobulbar palsy and ALS, and lower motor neuron lesions of cranial nerve XII can also be present in bulbar palsy and in ALS patients who also have lower motor neuron involvement. This article reviews these and other syndromes related to cranial nerves IX through XII that might be seen by psychiatry. PMID:20532157

  4. Cranial nerves of the coelacanth, Latimeria chalumnae [Osteichthyes: Sarcopterygii: Actinistia], and comparisons with other craniata.

    PubMed

    Northcutt, R G; Bemis, W E

    1993-01-01

    We reconstructed the cranial nerves of a serially sectioned prenatal coelacanth, Latimeria chalumnae. This allowed us to correct several mistakes in the literature and to make broad phylogenetic comparisons with other craniates. The genera surveyed in our phylogenetic analysis were Eptatretus, Myxine, Petromyzon, Lampetra, Chimaera, Hydrolagus, Squalus, Mustelus, Polypterus, Acipenser, Lepisosteus, Amia, Neoceratodus, Protopterus, Lepidosiren, Latimeria and Ambystoma. Cladistic analysis of our data shows that Latimeria shares with Ambystoma two characters of the cranial nerves. Our chief findings are: 1) Latimeria possesses an external nasal papilla and pedunculated olfactory bulbs but lacks a discrete terminal nerve. In other respects its olfactory system resembles the plesiomorphic pattern for craniates. 2) The optic nerve is plicated, a character found in many but not all gnathostomes. Latimeria retains an interdigitated partial decussation of the optic nerves, a character found in all craniates surveyed. 3) The oculomotor nerve supplies the same extrinsic eye muscles as in lampreys and gnathostomes. As in gnathostomes generally, Latimeria has a ciliary ganglion but its cells are located intracranially in the root of the oculomotor nerve, and their processes reach the eye via oculomotor and profundal rami. 4) The trochlear nerve supplies the superior oblique muscle as in all craniates that have not secondarily reduced the eye and its extrinsic musculature. 5) The profundal ganglion and ramus are entirely separate from the trigeminal system, with no exchange of fibers. This character has an interesting phylogenetic distribution: in hagfishes, lampreys, lungfishes and tetrapods, the profundal and trigeminal ganglia are fused, whereas in other taxa surveyed the ganglia are separate. The principal tissues innervated by the profundal nerve are the membranous walls of the tubes of the rostral organ. 6) As in lampreys and gnathostomes, the trigeminal nerve has

  5. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

  6. Retinal and optic nerve diseases.

    PubMed

    Margalit, Eyal; Sadda, Srinivas R

    2003-11-01

    A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device.

  7. Five Roots Pattern of Median Nerve Formation.

    PubMed

    Natsis, Konstantinos; Paraskevas, George; Tzika, Maria

    2016-01-01

    An unusual combination of median nerve's variations has been encountered in a male cadaver during routine educational dissection. In particular, the median nerve was formed by five roots; three roots originated from the lateral cord of the brachial plexus joined individually the median nerve's medial root. The latter (fourth) root was united with the lateral (fifth) root of the median nerve forming the median nerve distally in the upper arm and not the axilla as usually. In addition, the median nerve was situated medial to the brachial artery. We review comprehensively the relevant variants, their embryologic development and their potential clinical applications. PMID:27131354

  8. [Motor nerve hyperexcitability in ALS: its pathophysiology and treatment].

    PubMed

    Shibuya, Kazumoto; Misawa, Sonoko; Kuwabara, Satoshi

    2014-01-01

    Wide-spread fasciculations are prominent clinical features in patients with amyotrophic lateral sclerosis (ALS), specifically seen in ALS among disorders with neurogenic muscle atrophy. Fasciculations frequently arise from the motor nerve terminals, and the hyperexcitability of motor axons appears to constitute the pathophysiology of the disease. Neurophysiologic investigations of the upper and lower motor neurons/axons have shown increased excitability. The altered excitability is supposed to relate to motor neuron death. Based on these findings, a clinical trial of mexiletine (non-selective sodium channel blocker) is ongoing. PMID:25672715

  9. Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2

    SciTech Connect

    Yang, S.D.; Fong, Y.L.; Benovic, J.L.; Sibley, D.R.; Caron, M.G.; Lefkowitz, R.J.

    1988-06-25

    Recent evidence suggests that the function of receptors coupled to guanine nucleotide regulatory proteins may be controlled by highly specific protein kinases, e.g. rhodopsin kinase and the beta-adrenergic receptor kinase. In order to investigate the nature of the phosphatases which might be involved in controlling the state of receptor phosphorylation we studied the ability of four highly purified well characterized protein phosphatases to dephosphorylate preparations of rhodopsin or beta 2-adrenergic receptor which had been highly phosphorylated by beta-adrenergic receptor kinase. These included: type 1 phosphatase, calcineurin phosphatase, type 2A phosphatase, and the high molecular weight latent phosphatase 2. Under conditions in which all the phosphatases could dephosphorylate such common substrates as (/sup 32/P)phosphorylase a and (/sup 32/P)myelin basic protein at similar rates only the latent phosphatase 2 was active on the phosphorylated receptors. Moreover, a latent phosphatase activity was found predominantly in a sequestered membrane fraction of frog erythrocytes. This parallels the distribution of a beta-adrenergic receptor phosphatase activity recently described in these cells. These data suggest a potential role for the latent phosphatase 2 as a specific receptor phosphatase.

  10. Effects of thyroid hormone on. beta. -adrenergic responsiveness of aging cardiovascular systems

    SciTech Connect

    Tsujimoto, G.; Hashimoto, K.; Hoffman, B.B.

    1987-03-01

    The authors have compared the effects of ..beta..-adrenergic stimulation on the heart and peripheral vasculature of young (2-mo-old) and older (12-mo-old) rats both in the presence and absence of triiodothyronine (T/sub 3/)-induced hyperthyroidism. The hemodynamic consequences of T/sub 3/ treatment were less prominent in the aged hyperthyroid rats compared with young hyperthyroid rats (both in intact and pithed rats). There was a decrease in sensitivity of chronotropic responsiveness to isoproterenol in older pithed rats, which was apparently reversed by T/sub 3/ treatment. The number and affinity of myocardial ..beta..-adrenergic receptor sites measured by (/sup 125/I)cyanopindolol were not significantly different in young and older control rats; also, ..beta..-receptor density increased to a similar extent in both young and older T/sub 3/-treated rats. The ability of isoproterenol to relax mesenteric arterial rings, markedly blunted in older rats, was partially restored by T/sub 3/ treatment without their being any change in isoproterenol-mediated relaxation in the arterial preparation from young rats. The number and affinity of the ..beta..-adrenergic receptors measured in the mesenteric arteries was unaffected by either aging or T/sub 3/ treatment. The data suggest that effects of thyroid hormone and age-related alterations of cardiovascular responsiveness to ..beta..-adrenergic stimulation are interrelated in a complex fashion with a net result that the hyperkinetic cardiovascular manifestations in hyperthyroidism are attenuated in the older animals.

  11. Protein phosphorylation in isolated human adipocytes - Adrenergic control of the phosphorylation of hormone-sensitive lipase

    SciTech Connect

    Smiley, R.M. Columbia Univ College of Physicians and Surgeons, New York, NY ); Paul, S.; Browning, M.D.; Leibel, R.L.; Hirsch, J. )

    1990-01-01

    The effect of adrenergic agents on protein phosphorylation in human adipocytes was examined. Freshly isolated human fat cells were incubated with {sup 32}PO{sub 4} in order to label intracellular ATP, then treated with a variety of adrenergic and other pharmacologic agents. Treatment with the {beta}-adrenergic agonist isoproterenol led to a significant increase in phosphate content of at least five protein bands (M{sub r} 52, 53, 63, 67, 84 kDa). The increase in phosphorylation was partially inhibited by the {alpha}-2 agonist clonidine. Epinephrine, a combined {alpha} and {beta} agonist, was less effective at increasing phosphate content of the proteins than was isoproterenol. Neither insulin nor the {alpha}-1 agonist phenylephrine had any discernible effect on the pattern of protein phosphorylation. The 84 kDa phosphorylated peptide band appears to contain hormone-sensitive lipase, a key enzyme in the lipolytic pathway which is activated by phosphorylation. These results are somewhat different than previously reported results for rat adipocytes, and represent the first report of overall pattern and adrenergic modulation of protein phosphorylation in human adipocytes.

  12. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

    PubMed Central

    O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan

    2015-01-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and β-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and β-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of β-adrenergic receptors in regulating synaptic “tagging” and “capture” of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission. PMID:26286656

  13. The functional role of the alpha-1 adrenergic receptors in cerebral blood flow regulation.

    PubMed

    Purkayastha, Sushmita; Raven, Peter B

    2011-09-01

    Cerebral vasculature is richly innervated by the α-1 adrenergic receptors similar to that of the peripheral vasculature. However, the functional role of the α-1adrenergic receptors in cerebral blood flow (CBF) regulation is yet to be established. The traditional thinking being that during normotension and normocapnia sympathetic neural activity does not play a significant role in CBF regulation. Reports in the past have stated that catecholamines do not penetrate the blood brain barrier (BBB) and therefore only influence cerebral vessels from outside the BBB and hence, have a limited role in CBF regulation. However, with the advent of dynamic measurement techniques, beat-to-beat CBF assessment can be done during dynamic changes in arterial blood pressure. Several studies in the recent years have reported a functional role of the α-1adrenergic receptors in CBF regulation. This review focuses on the recent developments on the role of the sympathetic nervous system, specifically that of the α-1 adrenergic receptors in CBF regulation.

  14. α1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice.

    PubMed

    Ding, Fengfei; O'Donnell, John; Thrane, Alexander S; Zeppenfeld, Douglas; Kang, Hongyi; Xie, Lulu; Wang, Fushun; Nedergaard, Maiken

    2013-12-01

    Astrocyte Ca2+ signals in awake behaving mice are widespread, coordinated and differ fundamentally from the locally restricted Ca2+ transients observed ex vivo and in anesthetized animals. Here we show that the synchronized release of norepinephrine (NE) from locus coeruleus (LC) projections throughout the cerebral cortex mediate long-ranging Ca2+ signals by activation of astrocytic α1-adrenergic receptors. When LC output was triggered by either physiological sensory (whisker) stimulation or an air-puff startle response, astrocytes responded with fast Ca2+ transients that encompassed the entire imaged field (positioned over either frontal or parietal cortex). The application of adrenergic inhibitors, including α1-adrenergic antagonist prazosin, potently suppressed both evoked, as well as the frequently observed spontaneous astroglial Ca2+ signals. The LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which reduced cortical NE content by >90%, prevented nearly all astrocytic Ca2+ signals in awake mice. The observations indicate that in adult, unanesthetized mice, astrocytes do not respond directly to glutamatergic signaling evoked by sensory stimulation. Instead astrocytes appear to be the primary target for NE, with astrocytic Ca2+ signaling being triggered by the α1-adrenergic receptor. In turn, astrocytes may coordinate the broad effects of neuromodulators on neuronal activity.

  15. β-adrenergic signaling regulates evolutionarily derived sleep loss in the Mexican cavefish.

    PubMed

    Duboué, Erik R; Borowsky, Richard L; Keene, Alex C

    2012-01-01

    Sleep is a fundamental behavior exhibited almost universally throughout the animal kingdom. The required amount and circadian timing of sleep differs greatly between species in accordance with habitats and evolutionary history. The Mexican blind cavefish, Astyanax mexicanus, is a model organism for the study of adaptive morphological and behavioral traits. In addition to loss of eyes and pigmentation, cave populations of A. mexicanus exhibit evolutionarily derived sleep loss and increased vibration attraction behavior, presumably to cope with a nutrient-poor environment. Understanding the neural mechanisms of evolutionarily derived sleep loss in this system may reveal critical insights into the regulation of sleep in vertebrates. Here we report that blockade of β-adrenergic receptors with propranolol rescues the decreased-sleep phenotype of cavefish. This effect was not seen with α-adrenergic antagonists. Treatment with selective β1-, β2-, and β3-antagonists revealed that the increased sleep observed with propranolol could partially be explained via the β1-adrenergic system. Morphological analysis of catecholamine circuitry revealed conservation of gross catecholaminergic neuroanatomy between surface and cave morphs. Taken together, these findings suggest that evolutionarily derived changes in adrenergic signaling underlie the reduced sleep of cave populations. PMID:22922609

  16. β-adrenergic signaling regulates evolutionarily derived sleep loss in the Mexican cavefish.

    PubMed

    Duboué, Erik R; Borowsky, Richard L; Keene, Alex C

    2012-01-01

    Sleep is a fundamental behavior exhibited almost universally throughout the animal kingdom. The required amount and circadian timing of sleep differs greatly between species in accordance with habitats and evolutionary history. The Mexican blind cavefish, Astyanax mexicanus, is a model organism for the study of adaptive morphological and behavioral traits. In addition to loss of eyes and pigmentation, cave populations of A. mexicanus exhibit evolutionarily derived sleep loss and increased vibration attraction behavior, presumably to cope with a nutrient-poor environment. Understanding the neural mechanisms of evolutionarily derived sleep loss in this system may reveal critical insights into the regulation of sleep in vertebrates. Here we report that blockade of β-adrenergic receptors with propranolol rescues the decreased-sleep phenotype of cavefish. This effect was not seen with α-adrenergic antagonists. Treatment with selective β1-, β2-, and β3-antagonists revealed that the increased sleep observed with propranolol could partially be explained via the β1-adrenergic system. Morphological analysis of catecholamine circuitry revealed conservation of gross catecholaminergic neuroanatomy between surface and cave morphs. Taken together, these findings suggest that evolutionarily derived changes in adrenergic signaling underlie the reduced sleep of cave populations.

  17. Effects of Adrenergic Blockade on Postpartum Adaptive Responses Induced by Labor Contractions

    NASA Technical Reports Server (NTRS)

    Ronca, April E.; Mills, N. A.; Lam, K. P.; Hayes, L. E.; Bowley, Susan M. (Technical Monitor)

    2000-01-01

    Prenatal exposure to labor contractions augments the expression of postnatal adaptive responses in newborn rats. Near-term rat fetuses exposed prenatally to simulated labor contractions and delivered by cesarean section breath and attach to nipples at greater frequencies than non-stimulated fetuses. Plasma NE (norepinephrine) and EPI (epinephrine) was significantly elevated in newborn rats exposed to vaginal birth or simulated labor contractions (compressions) with cesarean delivery as compared to non-compressed fetuses. In the present study, we investigated adrenergic mechanisms underlying labor-induced postnatal adaptive responses. Following spinal transection of late pregnant rat dams, fetuses were administered neurogenic or non-neurogenic adrenergic blockade: 1) bretylium (10 mg/kg sc) to prevent sympathetic neuronal release, 2) hexamethonium (30 mg/kg) to produce ganglionic blockade, 3) phenoxybenzanune (10mg/kg sc), an a- adrenergic receptor antagonist, 4) ICI-118551, 10 mg/kg sc), a b receptor antagonist, or 5) vehicle alone. Fetuses were either compressed (C) or non-compressed (NC) prior to cesarean delivery. a- and b- adrenergic antagonists reduced respiration and nipple attachment rates while sympathetic and vehicle alone did not. These results provide additional support for the hypothesis that adaptive neonatal effects of labor contractions are mediated by adrenal and extra-adrenal catecholamines.

  18. Induction of functional beta-adrenergic receptors in HeLa cells.

    PubMed Central

    Tallman, J F; Smith, C C; Henneberry, R C

    1977-01-01

    HeLa cells contain beta-adrenergic receptors that are characterized by specific binding of I[3H]dihydroalprenolol, increased 3':5'-cyclic AMP production in intact cells after incubation with l-isoproterenol, and increased adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in the presence of l-isoproterenol. After cells were cultured with butyrate, the number of beta-adrenergic receptors, cyclic AMP production in intact cells, and adenylate cyclase activation by l-isoproterenol were increased severalfold over those of untreated cells. The increase involved the induction of synthesis of new receptor molecules with identical affinities for l-[3H]-dihydroalprenolol; all three processes were blocked by cycloheximide and actinomycin D. This induction was relatively specific for butyric acid and only the closely related short-chain fatty acids, propionic and valeric acids, were capable of partially inducing the same effect. In contrast to induction of beta-adrenergic binding sites, there was no increase in basal or fluoride-activated adenylate cyclase activity, indicating that the beta-adrenergic receptor and adenylate cyclase and different molecules that may be controlled separately. PMID:191837

  19. Alpha-1, alpha-2, and beta adrenergic signal transduction in cultured uterine myocytes.

    PubMed

    Phillippe, M; Saunders, T; Bangalore, S

    1990-04-01

    The following studies were undertaken to develop a cultured uterine myocyte model which would allow further clarification of the adrenergic signal transduction mechanisms utilized by these myocytes. After mechanical removal of the endometrium, rabbit uterine myocytes were isolated by an overnight enzymatic disaggregation using collagenase and DNase I. The isolated myocytes were maintained in culture in 75-cm2 flasks containing Waymouth's MB 751/1 medium-10% fetal bovine serum along with 10(-8) M estradiol, penicillin, streptomycin, and Fungizone. The phase contrast and electron micrographic appearance of these cells was consistent with that previously reported for smooth muscle myocytes in culture. Immunocytochemical studies utilizing monoclonal anti-alpha-smooth muscle actin antibodies confirmed the presence of smooth muscle actin in these cultured myocytes. Western blot studies similarly confirmed the presence of alpha-smooth muscle actin in rabbit myometrial tissue and the cultured myocytes, both the primary and F1 generation. After prelabeling the myocytes with [3H]inositol, adrenergic stimulation experiments demonstrated alpha-1 receptor mediated stimulation of inositol phosphates. Beta receptor stimulation experiments confirmed cAMP production in these cultured myocytes, and the ability of clonidine, an alpha-2 agonist, to inhibit forskolin stimulated cAMP production confirmed the presence of functional alpha-2 adrenergic receptors in these myocytes. In conclusion, these cultured rabbit uterine myocytes have provided an in vitro model which can be utilized to further clarify the adrenergic receptor signal transduction mechanisms in genital tract smooth muscle.

  20. Facial nerve paralysis in children.

    PubMed

    Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

    2015-12-16

    Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID:26677445

  1. Facial nerve paralysis in children

    PubMed Central

    Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

    2015-01-01

    Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology. PMID:26677445

  2. Facial nerve paralysis in children.

    PubMed

    Ciorba, Andrea; Corazzi, Virginia; Conz, Veronica; Bianchini, Chiara; Aimoni, Claudia

    2015-12-16

    Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology.

  3. Embryonic anastomosis between hypoglossal nerves.

    PubMed

    Rodríguez-Vázquez, J F; Mérida-Velasco, J R; Verdugo-López, S; Sanz-Casado, J V; Jiménez-Collado, J

    2009-12-01

    This article presents two cases of anastomosis of hypoglossal nerves in the suprahyoid region in human embryos of CR length 10.75 and 17.5 mm. This variation was studied in two human specimens at this stage of development and compared with the normal arrangement of the hypoglossal nerves in embryos at the same stage. The anastomotic branches were of similar caliber to the main trunks. In both cases the anastomosis was located dorsal to the origin of the geniohyoid muscles and caudal to the genioglossus muscles, lying transversally over the cranial face of the body of the hyoid bone anlage. The anastomosis formed a suprahyoid nerve chiasm on the midline in the embryo of 10.75 mm CR length.

  4. β-adrenergic receptor mediation of stress-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: roles for β1 and β2 adrenergic receptors.

    PubMed

    Vranjkovic, Oliver; Hang, Shona; Baker, David A; Mantsch, John R

    2012-08-01

    Stress can trigger the relapse of drug use in recovering cocaine addicts and reinstatement in rodent models through mechanisms that may involve norepinephrine release and β-adrenergic receptor activation. The present study examined the role of β-adrenergic receptor subtypes in the stressor-induced reinstatement of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in mice. Forced swim (6 min at 22°C) stress or activation of central noradrenergic neurotransmission by administration of the selective α(2) adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement in wild-type, but not β- adrenergic receptor-deficient Adrb1/Adrb2 double-knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in reinstatement in both wild-type and β-adrenergic receptor knockout mice. Stress-induced reinstatement probably involved β(2) adrenergic receptors. The β(2) adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by forced swim or BRL-44,408, whereas administration of the nonselective β-adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the β(2) adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the β(1) adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a potential cooperative role for β(1) and β(2) adrenergic receptors in stress-induced reinstatement. Overall, these findings suggest that targeting β-adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse, particularly in cocaine addicts whose drug use

  5. Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.

    PubMed

    Sikirić, P; Mazul, B; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Gjurasin, M; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Miklić, P; Sumajstorcić, J

    1997-03-01

    Since superior protection against different gastrointestinal and liver lesions and antiinflammatory and analgesic activities were noted for pentadecapeptide BPC (an essential fragment of an organoprotective gastric juice protein named BPC), the beneficial mechanism of BPC 157 and its likely interactions with other systems were studied. Hence its beneficial effects would be abolished by adrenal gland medullectomy, the influence of different agents affecting alpha, beta, and dopamine receptors on BPC 157 gastroprotection in 48 h restraint stress was further investigated. Animals were pretreated (1 hr before stress) with saline (controls) or BPC 157 (dissolved in saline) (10 microg or 10 ng/kg body wt intraperitoneally or intragastrically) applied either alone to establish basal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneous administration was carried out with various agents with specific effects on adrenergic or dopaminergic receptors [given in milligrams per kilogram intraperitoneally except for atenolol, which was given subcutaneously] phentolamine (10.0), prazosin (0.5), yohimbine (5.0), clonidine (0.1) (alpha-adrenergic domain), propranolol (1.0), atenolol (20.0) (beta-adrenergic domain), domperidone (5.0), and haloperidol (5.0) (peripheral/central dopamine system). Alternatively, agents stimulating adrenergic or dopaminergic systems--adrenaline (5.0) or bromocriptine (10.0)--were applied. A strong protection, noted following intragastric or intraperitoneal administration of BPC 157, was fully abolished by coadministration of phentolamine, clonidine, and haloperidol, and consistently not affected by prazosin, yohimbine, or domperidone. Atenolol abolished only intraperitoneal BPC 157 protection, whereas propranolol affected specifically intragastric BPC 157 protection. Interestingly, the severe course of lesion development obtained in basal conditions, unlike BPC 157 gastroprotection, was not influenced by the application of

  6. Rehabilitation of peripheral nerve injuries.

    PubMed

    Robinson, Michael D; Shannon, Steven

    2002-02-01

    Traumatic injuries to peripheral nerves pose complex challenges to both military and civilian physicians. Treatment of nerve injuries must consider all aspects of the inherent disability. Pain control is of paramount importance. Little will be accomplished until pain is brought down to tolerable levels. Rehabilitation needs to be instituted as first-line treatment. Focus must be first placed on protection of the affected area from complications stemming from disuse and immobility and then on enhancement of strength, flexibility, sensory discrimination, and dexterity. Early intervention sets the stage for optimal physiologic and functional recovery. PMID:11878078

  7. Nerve lesioning with direct current

    NASA Astrophysics Data System (ADS)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  8. Peripheral nerve disease in pregnancy.

    PubMed

    Klein, Autumn

    2013-06-01

    Neuropathies during pregnancy and the postpartum period are common and are usually due to compression around pregnancy and childbirth. The most common peripheral neuropathies are Bell's palsy, carpal tunnel syndrome (CTS), and lower extremity neuropathies. Although most neuropathies are usually reversible, associated disabilities or morbidities can limit functioning and require therapy. Nerve conduction study tests and imaging should only be considered if symptoms are unusual or prolonged. Some neuropathies may be associated with preeclampsia or an inherent underlying neuropathy that increases the risk of nerve injury. All neuropathies in pregnancy should be followed as some may be persistent and require follow-up. PMID:23563878

  9. Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats.

    PubMed

    Lyon, Timothy D; Ferroni, Matthew C; Kadow, Brian T; Slater, Richard C; Zhang, Zhaocun; Chang, Victor; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-02-15

    This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under α-chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective β-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P < 0.05) reduced the amplitude and area under the curve of the bladder contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a β-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders. PMID:26676253

  10. Phenylethynyl terminated imide oligomers

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Havens, Stephen J. (Inventor)

    1995-01-01

    Four phenylethynyl amine compounds - 3 and 4-aminophenoxy-4'-phenylethynylbenzophenone, and 3 and 4-amino-4'-phenylethynylbenzophenone - were readily prepared and were used to endcap imide oligomers. Phenylethynyl-terminated amide acid oligomers and phenylethynyl-terminated imide oligomers with various molecular weights and compositions were prepared and characterized. These oligomers were cured at 300 to 400 C to provide crosslinked polyimides with excellent solvent resistance, high strength and modulus, and good high temperature properties. Adhesive panels, composites, films, and moldings from these phenylethynyl terminated imide oligomers gave excellent mechanical performance.

  11. Nonrecurrent Laryngeal Nerve in the Era of Intraoperative Nerve Monitoring

    PubMed Central

    Gurleyik, Gunay

    2016-01-01

    Nonrecurrent laryngeal nerve (non-RLN) is an anatomical variation increasing the risk of vocal cord palsy. Prediction and early identification of non-RLN may minimize such a risk of injury. This study assessed the effect of intraoperative neuromonitoring (IONM) on the detection of non-RLN. A total of 462 (236 right) nerves in 272 patients were identified and totally exposed, and all intraoperative steps of IONM were sequentially applied on the vagus nerve (VN) and RLN. Right predissection VN stimulation at a distal point did not create a sound signal in three cases (3/236; 1.27%). Proximal dissection of the right VN under IONM guidance established a proximal point, creating a positive signal. The separation point of non-RLN from VN was discovered in all three patients. Non-RLNs were exposed from separation to laryngeal entry. Positive IONM signals were obtained after resection of thyroid lobes, and postoperative period was uneventful in patients with non-RLN. Absence of distal VN signal is a precise predictor of the non-RLN. IONM-guided proximal dissection of the right VN leads to identification of the non-RLN. The prediction of non-RLN by the absence of the VN signal at an early stage of surgery may prevent or minimize the risk of nerve injury.

  12. Astrocytic β2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice

    PubMed Central

    Jensen, Cathy Joanna; Demol, Frauke; Bauwens, Romy; Kooijman, Ron; Massie, Ann; Villers, Agnès; Ris, Laurence; De Keyser, Jacques

    2016-01-01

    In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the β2-adrenergic receptor on astrocytes might contribute to this energy balance, it has not yet been shown conclusively in vivo. Inducible astrocyte specific β2-adrenergic receptor knock-out mice were generated by crossing homozygous β2-adrenergic receptor floxed mice (Adrb2flox) and mice with heterozygous tamoxifen-inducible Cre recombinase-expression driven by the astrocyte specific L-glutamate/L-aspartate transporter promoter (GLAST-CreERT2). Assessments using the modified SHIRPA (SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment) test battery, swimming ability test, and accelerating rotarod test, performed at 1, 2 and 4 weeks, 6 and 12 months after tamoxifen (or vehicle) administration did not reveal any differences in physical health or motor functions between the knock-out mice and controls. However deficits were found in the cognitive ability of aged, but not young adult mice, reflected in impaired learning in the Morris Water Maze. Similarly, long-term potentiation (LTP) was impaired in hippocampal brain slices of aged knock-out mice maintained in low glucose media. Using microdialysis in cerebellar white matter we found no significant differences in extracellular lactate or glucose between the young adult knock-out mice and controls, although trends were detected. Our results suggest that β2-adrenergic receptor expression on astrocytes in mice may be important for maintaining cognitive health at advanced age, but is dispensable for motor function. PMID:27776147

  13. α1B-adrenergic receptors differentially associate with Rab proteins during homologous and heterologous desensitization.

    PubMed

    Castillo-Badillo, Jean A; Sánchez-Reyes, Omar B; Alfonzo-Méndez, Marco A; Romero-Ávila, M Teresa; Reyes-Cruz, Guadalupe; García-Sáinz, J Adolfo

    2015-01-01

    Internalization of G protein-coupled receptors can be triggered by agonists or by other stimuli. The process begins within seconds of cell activation and contributes to receptor desensitization. The Rab GTPase family controls endocytosis, vesicular trafficking, and endosomal fusion. Among their remarkable properties is the differential distribution of its members on the surface of various organelles. In the endocytic pathway, Rab 5 controls traffic from the plasma membrane to early endosomes, whereas Rab 4 and Rab 11 regulate rapid and slow recycling from early endosomes to the plasma membrane, respectively. Moreover, Rab 7 and Rab 9 regulate the traffic from late endosomes to lysosomes and recycling to the trans-Golgi. We explore the possibility that α1B-adrenergic receptor internalization induced by agonists (homologous) and by unrelated stimuli (heterologous) could involve different Rab proteins. This possibility was explored by Fluorescence Resonance Energy Transfer (FRET) using cells coexpressing α1B-adrenergic receptors tagged with the red fluorescent protein, DsRed, and different Rab proteins tagged with the green fluorescent protein. It was observed that when α1B-adrenergic receptors were stimulated with noradrenaline, the receptors interacted with proteins present in early endosomes, such as the early endosomes antigen 1, Rab 5, Rab 4, and Rab 11 but not with late endosome markers, such as Rab 9 and Rab 7. In contrast, sphingosine 1-phosphate stimulation induced rapid and transient α1B-adrenergic receptor interaction of relatively small magnitude with Rab 5 and a more pronounced and sustained one with Rab 9; interaction was also observed with Rab 7. Moreover, the GTPase activity of the Rab proteins appears to be required because no FRET was observed when dominant-negative Rab mutants were employed. These data indicate that α1B-adrenergic receptors are directed to different endocytic vesicles depending on the desensitization type (homologous vs

  14. Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion.

    PubMed

    León-Velarde, F; Bourin, M C; Germack, R; Mohammadi, K; Crozatier, B; Richalet, J P

    2001-01-01

    Norepinephrine (NE)-induced desensitization of the adrenergic receptor pathway may mimic the effects of hypoxia on cardiac adrenoceptors. The mechanisms involved in this desensitization were evaluated in male Wistar rats kept in a hypobaric chamber (380 Torr) and in rats infused with NE (0.3 mg. kg(-1). h(-1)) for 21 days. Because NE treatment resulted in left ventricular (LV) hypertrophy, whereas hypoxia resulted in right (RV) hypertrophy, the selective hypertrophic response of hypoxia and NE was also evaluated. In hypoxia, alpha(1)-adrenergic receptors (AR) density increased by 35%, only in the LV. In NE, alpha(1)-AR density decreased by 43% in the RV. Both hypoxia and NE decreased beta-AR density. No difference was found in receptor apparent affinity. Stimulated maximal activity of adenylate cyclase decreased in both ventricles with hypoxia (LV, 41%; RV, 36%) but only in LV with NE infusion (42%). The functional activities of G(i) and G(s) proteins in cardiac membranes were assessed by incubation with pertussis toxin (PT) and cholera toxin (CT). PT had an important effect in abolishing the decrease in isoproterenol-induced stimulation of adenylate cyclase in hypoxia; however, pretreatment of the NE ventricle cells with PT failed to restore this stimulation. Although CT attenuates the basal activity of adenylate cyclase in the RV and the isoproterenol-stimulated activity in the LV, pretreatment of NE or hypoxic cardiac membranes with CT has a less clear effect on the adenylate cyclase pathway. The present study has demonstrated that 1) NE does not mimic the effects of hypoxia at the cellular level, i.e., hypoxia has specific effects on cardiac adrenergic signaling, and 2) changes in alpha- and beta-adrenergic pathways are chamber specific and may depend on the type of stimulation (hypoxia or adrenergic).

  15. Beta 2-adrenergic receptor regulation of human neutrophil function is sexually dimorphic.

    PubMed

    de Coupade, Catherine; Gear, Robert W; Dazin, Paul F; Sroussi, Herve Y; Green, Paul G; Levine, Jon D

    2004-12-01

    While the mechanisms underlying the marked sexual dimorphism in inflammatory diseases are not well understood, the sexually dimorphic sympathoadrenal axis profoundly affects the inflammatory response. We tested whether adrenergic receptor-mediated activation of human neutrophil function is sexually dimorphic, since neutrophils provide the first line of defense in the inflammatory response. There was a marked sexual dimorphism in beta(2)-adrenergic receptor binding, using the specific beta(2)-adrenergic receptor ligand, [(3)H]-dihydroalprenolol, with almost three times more binding sites on neutrophils from females (20,878 +/- 2470) compared to males (7331 +/- 3179). There was also a marked sexual dimorphism in the effects of isoprenaline, a beta-adrenergic receptor agonist, which increased nondirected locomotion (chemokinesis) in neutrophils obtained from females, while having no effect on neutrophils from males. Isoprenaline stimulated the release of a chemotactic factor from neutrophils obtained from females, but not from males. This chemotactic factor acts on the G protein-coupled CXC chemokine receptor 2 (CXCR2) chemokine receptor, since an anti-CXCR2 antibody and the selective nonpeptide CXCR2 antagonist SB225002, inhibited chemotaxis produced by this factor. While interleukin- (IL-) 8 is a principal CXCR2 ligand, isoprenaline did not produce an increase in IL-8 release from neutrophils. IL-8-induced chemotaxis was inhibited in a sexually dimorphic manner by isoprenaline, which also stimulated release of a mediator from neutrophils that induced chemotaxis, that was inhibited by anti-CXCR2 antibodies. These findings indicate an important role for adrenergic receptors in the modulation of neutrophil trafficking, which could contribute to sex-differences in the inflammatory response. PMID:15477226

  16. α1B-Adrenergic Receptors Differentially Associate with Rab Proteins during Homologous and Heterologous Desensitization

    PubMed Central

    Castillo-Badillo, Jean A.; Sánchez-Reyes, Omar B.; Alfonzo-Méndez, Marco A.; Romero-Ávila, M. Teresa; Reyes-Cruz, Guadalupe; García-Sáinz, J. Adolfo

    2015-01-01

    Internalization of G protein-coupled receptors can be triggered by agonists or by other stimuli. The process begins within seconds of cell activation and contributes to receptor desensitization. The Rab GTPase family controls endocytosis, vesicular trafficking, and endosomal fusion. Among their remarkable properties is the differential distribution of its members on the surface of various organelles. In the endocytic pathway, Rab 5 controls traffic from the plasma membrane to early endosomes, whereas Rab 4 and Rab 11 regulate rapid and slow recycling from early endosomes to the plasma membrane, respectively. Moreover, Rab 7 and Rab 9 regulate the traffic from late endosomes to lysosomes and recycling to the trans-Golgi. We explore the possibility that α1B-adrenergic receptor internalization induced by agonists (homologous) and by unrelated stimuli (heterologous) could involve different Rab proteins. This possibility was explored by Fluorescence Resonance Energy Transfer (FRET) using cells coexpressing α1B-adrenergic receptors tagged with the red fluorescent protein, DsRed, and different Rab proteins tagged with the green fluorescent protein. It was observed that when α1B-adrenergic receptors were stimulated with noradrenaline, the receptors interacted with proteins present in early endosomes, such as the early endosomes antigen 1, Rab 5, Rab 4, and Rab 11 but not with late endosome markers, such as Rab 9 and Rab 7. In contrast, sphingosine 1-phosphate stimulation induced rapid and transient α1B-adrenergic receptor interaction of relatively small magnitude with Rab 5 and a more pronounced and sustained one with Rab 9; interaction was also observed with Rab 7. Moreover, the GTPase activity of the Rab proteins appears to be required because no FRET was observed when dominant-negative Rab mutants were employed. These data indicate that α1B-adrenergic receptors are directed to different endocytic vesicles depending on the desensitization type (homologous vs

  17. α1B-adrenergic receptors differentially associate with Rab proteins during homologous and heterologous desensitization.

    PubMed

    Castillo-Badillo, Jean A; Sánchez-Reyes, Omar B; Alfonzo-Méndez, Marco A; Romero-Ávila, M Teresa; Reyes-Cruz, Guadalupe; García-Sáinz, J Adolfo

    2015-01-01

    Internalization of G protein-coupled receptors can be triggered by agonists or by other stimuli. The process begins within seconds of cell activation and contributes to receptor desensitization. The Rab GTPase family controls endocytosis, vesicular trafficking, and endosomal fusion. Among their remarkable properties is the differential distribution of its members on the surface of various organelles. In the endocytic pathway, Rab 5 controls traffic from the plasma membrane to early endosomes, whereas Rab 4 and Rab 11 regulate rapid and slow recycling from early endosomes to the plasma membrane, respectively. Moreover, Rab 7 and Rab 9 regulate the traffic from late endosomes to lysosomes and recycling to the trans-Golgi. We explore the possibility that α1B-adrenergic receptor internalization induced by agonists (homologous) and by unrelated stimuli (heterologous) could involve different Rab proteins. This possibility was explored by Fluorescence Resonance Energy Transfer (FRET) using cells coexpressing α1B-adrenergic receptors tagged with the red fluorescent protein, DsRed, and different Rab proteins tagged with the green fluorescent protein. It was observed that when α1B-adrenergic receptors were stimulated with noradrenaline, the receptors interacted with proteins present in early endosomes, such as the early endosomes antigen 1, Rab 5, Rab 4, and Rab 11 but not with late endosome markers, such as Rab 9 and Rab 7. In contrast, sphingosine 1-phosphate stimulation induced rapid and transient α1B-adrenergic receptor interaction of relatively small magnitude with Rab 5 and a more pronounced and sustained one with Rab 9; interaction was also observed with Rab 7. Moreover, the GTPase activity of the Rab proteins appears to be required because no FRET was observed when dominant-negative Rab mutants were employed. These data indicate that α1B-adrenergic receptors are directed to different endocytic vesicles depending on the desensitization type (homologous vs

  18. Sensory cutaneous nerve fine-needle aspiration in Hansen's disease: A retrospective analysis of our experience

    PubMed Central

    Prasoon, Dev; Mandal, Swapan Kumar; Agrawal, Parimal

    2015-01-01

    Background: Leprosy affects peripheral nerves. As Mycobacterium leprae has unique tropism for Schwann cells, thickened sensory cutaneous nerves provide an easy target for the detection of lepra bacilli and other changes associated with the disease. Materials and Methods: The data of patients with sensory cutaneous nerve involvement were retrieved from our record for the period January 2006 to December 2014. The hematoxylin and eosin (H and E)- and May-Grünwald-Giemsa (MGG)-stained slides were screened for Schwann cells, granuloma, and necrosis. Modified Ziehl-Neelsen (ZN)-stained smears were searched for lepra bacilli and globi. Morphological index was calculated in multibacillary lesions. Result: Twenty-nine sensory cutaneous nerves were aspirated in 23 patients. While 15 cases showed skin and nerve involvement, 8 cases showed only nerve involvement. Terminal cutaneous branch of the radial nerve was most often aspirated. No motor loss was observed after aspiration. Five cytologic pictures were seen — Epithelioid cell granuloma only in 6 cases, epithelioid cell granuloma with necrosis in 1 case, epithelioid cell granuloma with lepra bacilli in 3 cases, necrosis with lepra bacilli in 1 case, and only lepra bacilli in 12 cases. Morphological index ranged from 20% to 80%. Conclusion: Sensory cutaneous nerve fine-needle aspiration (FNA) is a feasible, viable, effective, and safe procedure. It adds to diagnostic FNA yield in patients with concomitant skin involvement and offers a way to evaluate patients with only nerve involvement. Calculation of morphological index allows prognostication and may have a role in assessing response to therapy and/or relapse. PMID:26729977

  19. The trophic influence of tetrodotoxin-inactive nerves on normal and reinnervated rat skeletal muscles.

    PubMed Central

    Bray, J J; Hubbard, J I; Mills, R G

    1979-01-01

    1. Nerve impulses in the rat sciatic nerve were blocked for long periods by tetrodotoxin (TTX) released from capillary implants. The TTX capillaries did not block axonal transport, nor did they cause any sign of nerve degeneration. 2. A comparison of the effects of TTX paralysis and denervation was made on both extensor digitorium longus (e.d.l.) and soleus muscles over 21 days, a time when the products of nerve degeneration were unlikely to contribute to the changes associated with denervation. The resting membrane potential of TTX-paralysed muscles was significantly different (P less than 0.005) from that of the denervated muscles at all periods and at 21 days the decrease that can be attributed to inactivity was 61% (e.d.l.) and 49% (soleus) of that which follows denervation. This disparity was even more pronounced for the ACh receptor density where the increase in receptors due to inactivity was only 34% (e.d.l.) and 21% (soleus) of that due to denervation. 3. A similar comparison was made on muscles which had been reinnervated by TTX-inactive nerves. These muscles were found to have a significantly higher resting membrane potential and lower ACh receptor density than the denervated muscles (P less than 0.05). 4. The experiments on reinnervated muscles preclude the possibility that nerve degeneration products are solely responsible for the difference between the TTX-paralysed and denervated muscles and suggest that the difference can be attributed to the trophic influence of the nerve. 5. An observed increase in the m.e.p.p. frequency of the TTX-paralysed muscles indicated that nerve action potentials play a role in regulating the spontaneous release from nerve terminals. PMID:94092

  20. Sail intelligent terminal evaluation

    NASA Technical Reports Server (NTRS)

    Pruitt, J. L.

    1977-01-01

    Engineering assessments, recommendations, and equipment necessary to solve the operational problems are described, and operational flexibility of the intelligent terminal facility are extended. The following capabilities were considered: (1) the operation of at least two D/D stations and one remote graphics terminal simultaneously; (2) the capability to run plotter, AIDS and FORTRAN programs simultaneously; (3) simultaneous use of system utility routines of D/D stations and remote graphics terminal; (4) the capability to provide large volume hardcopy of data and graphics; and (5) the capability to eliminate or at least ease the current operation/programming problems with related labor costs. The overall intelligent terminal development, and plans guiding the analysis and equipment acquisitions were studied, and the assessments and analyses performed are also summarized.

  1. Nearest Alignment Space Termination

    2006-07-13

    Near Alignment Space Termination (NAST) is the Greengenes algorithm that matches up submitted sequences with the Greengenes database to look for similarities and align the submitted sequences based on those similarities.

  2. Proximal Sciatic Nerve Intraneural Ganglion Cyst

    PubMed Central

    Swartz, Karin R.; Wilson, Dianne; Boland, Michael; Fee, Dominic B.

    2009-01-01

    Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009. PMID:20069041

  3. Patterned substrates and methods for nerve regeneration

    DOEpatents

    Mallapragada, Surya K.; Heath, Carole; Shanks, Howard; Miller, Cheryl A.; Jeftinija, Srdija

    2004-01-13

    Micropatterned substrates and methods for fabrication of artificial nerve regeneration conduits and methods for regenerating nerves are provided. Guidance compounds or cells are seeded in grooves formed on the patterned substrate. The substrates may also be provided with electrodes to provide electrical guidance cues to the regenerating nerve. The micropatterned substrates give physical, chemical, cellular and/or electrical guidance cues to promote nerve regeneration at the cellular level.

  4. Anatomy and physiology of neurons composing the commissural ring nerve of the cricket, Acheta domesticus.

    PubMed

    Killian, K A; Bollins, J P; Govind, C K

    2000-03-01

    The commissural ring nerve (RN) of the cricket Acheta domesticus links together the two cercal motor nerves of the terminal abdominal ganglion. It contains the axons of almost 100 neurons including two bilateral clusters of eight to 13 ventrolateral neurons and approximately 75 neurons with midline somata within the terminal abdominal ganglion. The ventrolateral neurons have an ipsilateral dendritic arborization within the dorsal neuropil of the ganglion and their axons use the RN as a commissure in order to enter the contralateral nerves of the tenth ganglionic neuromere. In contrast, most midline neurons have bifurcating axons projecting bilaterally into the neuropil of the ganglion as well as into the RN where they often branch extensively before entering the contralateral tenth nerves. Most RN neurons have small, non-spiking somata with spike initiation zones distant from the soma. Many midline neurons also produce double-peaked spikes in their somata, indicative of multiple spike initiation zones. Spontaneous neuronal activity recorded extracellularly from the RN reveals several units, some with variable firing patterns, but none responding to sensory stimuli. The RN is primarily composed of small (50 nm diameter) axon profiles with a few large (0.5-1 microm diameter) profiles. Occasionally, profiles of nerve terminals containing primarily small clear vesicles and a few large dense vesicles are observed. These vesicles can sometimes be clustered about an active zone. We conclude that the primary function of the RN is to serve as a peripheral nerve commissure and that its role as a neurohemal organ is negligible. J. Exp. Zool. 286:350-366, 2000.

  5. Effect of Artificial Nerve Conduit Vascularization on Peripheral Nerve in a Necrotic Bed

    PubMed Central

    Iijima, Yuki; Murayama, Akira; Takeshita, Katsushi

    2016-01-01

    Background: Several types of artificial nerve conduit have been used for bridging peripheral nerve gaps as an alternative to autologous nerves. However, their efficacy in repairing nerve injuries accompanied by surrounding tissue damage remains unclear. We fabricated a novel nerve conduit vascularized by superficial inferior epigastric (SIE) vessels and evaluated whether it could promote axonal regeneration in a necrotic bed. Methods: A 15-mm nerve conduit was implanted beneath the SIE vessels in the groin of a rat to supply it with blood vessels 2 weeks before nerve reconstruction. We removed a 13-mm segment of the sciatic nerve and then pressed a heated iron against the dorsal thigh muscle to produce a burn. The defects were immediately repaired with an autograft (n = 10), nerve conduit graft (n = 8), or vascularized nerve conduit graft (n = 8). Recovery of motor function was examined for 18 weeks after surgery. The regenerated nerves were electrophysiologically and histologically evaluated. Results: The vascularity of the nerve conduit implanted beneath the SIE vessels was confirmed histologically 2 weeks after implantation. Between 14 and 18 weeks after surgery, motor function of the vascularized conduit group was significantly better than that of the nonvascularized conduit group. Electrophysiological and histological evaluations revealed that although the improvement did not reach the level of reinnervation achieved by an autograft, the vascularized nerve conduit improved axonal regeneration more than did the conduit alone. Conclusion: Vascularization of artificial nerve conduits accelerated peripheral nerve regeneration, but further research is required to improve the quality of nerve regeneration. PMID:27257595

  6. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

    PubMed Central

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-01-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porci