UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of GABA and of drugs, known to alter GABA-metabolism, on the hypovolaemia-provoked vasopressin release was investigated in rats. Blood volume was decreased without altering plasma osmolality or arterial blood pressure by i.p. injection of polyethylene glycol and the resulting plasma vasopressin concentration was measured using a radioimmunoassay. I.c.v. injections of GABA (0.4-2 mg) markedly suppressed the hypovolaemia-induced vasopressin release. The central inhibitory effect of GABA could not be related to appropriate changes in peripheral parameters believed to regulate vasopressin release (arterial blood pressure, renin-angiotensin system). Aminooxyacetic acid (9-81 mg kg-1, i.m.) and gamma-vinyl-GABA (1.5 g kg-1, i.p.), two potent inhibitors of GABA aminotransferase and known to increase brain GABA content, reduced vasopressin release to a comparable degree as did GABA (i.c.v.). On the other hand, 3-mercaptopropionic acid (10-90 mg kg-1, i.p.), an inhibitor of the GABA synthetizing enzyme glutamic acid decarboxylase, promoted the release of vasopressin when the rats were killed prior to the onset of convulsions. These results, on the whole, intimate the existence of a GABA-mediated inhibition in the central control of vasopressin release.
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PMID:Evidence for the involvement of a GABA-mediated inhibition in the hypovolaemia-induced vasopressin release. 719 56

The inhibitory neurotransmitter GABA plays an important role in regulating the activity of magnocellular oxytocin and vasopressin neurons located in the supraoptic and paraventricular nuclei through occupancy of GABAA receptors. However, the GABAA receptor is a hetero-oligomeric protein comprised of different subunits and the subunit types expressed in a given receptor complex appear critical for its sensitivity to GABA, benzodiazepines and/or steroids. Thus, in order to understand fully the GABAergic control of oxytocin and vasopressin secretion, definition of the GABAA receptors synthesized by magnocellular neurons in the supraoptic and paraventricular nuclei is required. In the supraoptic nucleus, antibodies directed against the alpha 1, alpha 2 and beta 2/3 subunits of the GABAA receptor revealed similar strong antigen distribution on all magnocellular neurons. Using sequential double-immunoperoxidase staining, immunoreactivity for all three subunits was observed on both oxytocin and vasopressin neurons of the supraoptic nucleus. In contrast, only alpha 2 subunit immunoreactivity was detected on the cell bodies of oxytocin and vasopressin neurons in the paraventricular nucleus. No sex differences were detected. In situ hybridization experiments using 35S-labelled oligonucleotides showed that all supraoptic neurons expressed alpha 1, alpha 2 and beta 2 subunit messenger RNA transcripts while magnocellular neurons in the paraventricular nucleus were only enriched in alpha 2 subunit messenger RNA. Quantitative analysis showed that the expression of alpha 1 and beta 2 subunit messenger RNAs in the paraventricular nucleus was half that observed in the supraoptic nucleus while expression of beta 3 subunit messenger RNA was very low in both nuclei. These results show that all oxytocin and vasopressin neurons located in the supraoptic nucleus synthesize and express alpha 1, alpha 2 and beta 2 subunits of the GABAA receptor while those in the paraventricular nucleus are only immunoreactive for the alpha 2 subunit. These observations suggest, therefore, that at least two pharmacologically distinct GABAA receptor isoforms exist on supraoptic neurons and that these are different to those expressed by paraventricular magnocellular cells. Thus, in addition to providing a definition of the subunits likely to form specific GABAA receptor isoforms on magnocellular neurons, this study gives direct evidence for GABAA receptor heterogeneity between supraoptic and paraventricular neurons, but not between oxytocin and vasopressin cells.
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PMID:Cellular localization and differential distribution of GABAA receptor subunit proteins and messenger RNAs within hypothalamic magnocellular neurons. 775 80

The magnocellular neurons of the rat supraoptic nucleus were investigated by using (a) the patch-clamp technique on thin brain slice preparations to demonstrate voltage- and GABA-activated ionic currents, and (b) immunohistochemistry to demonstrate the expression of the beta 2 and beta 3 subunits of the GABAA-receptor on their membrane surface and the contents of the neuropeptides vasopressin and oxytocin. During electrophysiological recording in the whole-cell mode neurons were stained with Lucifer Yellow and camera lucida drawings were made. Two types of neurons could be distinguished by their different K(+)-currents, an inactivating and a noninactivating type. All neurons had a fast Na+ inward current. GABAA-activated currents were characterized by investigation of their ionic conductance and by blocking experiments with the GABAA-antagonist bicuculline.
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PMID:Patch-clamp study of membrane properties and GABA-activated currents of rat magnocellular supraoptic neurons in thin slice preparation. 781 98

To assess whether GABA given intracerebroventricularly (i.c.v.) affects vasopressin (AVP) and atrial natriuretic peptide (ANP) release and changes in blood pressure in response to i.c.v. angiotensin (AT II) and carbachol (CB), or whether changes in blood pressure affect GABA release in the brain, experiments were carried out. In experiment I (Ex I), GABA (100 micrograms) with AT II (50 ng) or CB (25 ng) was i.c.v. administered in conscious rats (n = 12). The same dose of AT II or CB alone also was administered without GABA (n = 12). In experiment II (Ex II), AT II (100 ng/kg per min) or nitropuruside (NP, 10 micrograms/kg per min) was intravenously (i.v.) infused and GABA release in the area adjacent to the paraventricular nucleus was determined, using the microdialysis method, in conscious rats (n = 12). In the experiments, mean arterial blood pressure (MABP), heart rate (HR), plasma AVP and/or ANP and plasma Na+ and K+ levels were measured. In Ex I, i.c.v. AT II increased plasma AVP and MABP without changes in HR and plasma ANP, but i.c.v. GABA never affected these responses. Icv CB also increased plasma AVP and MABP with decreased HR, but did not affect plasma ANP. Icv GABA abolished bradycardiac responses, but did not affect the others. In Ex II, the pressor response to i.v. AT II increased GABA release without apparent decreases in plasma AVP. However, the depressor response to NP produced decreases in GABA release with increased plasma AVP. These results shows that i.c.v. GABA did not affect AVP and pressor responses to i.c.v. AT II and CB, but changes in blood pressure modulates GABA release in the brain with changes in plasma AVP.
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PMID:The role of GABA in the central regulation of AVP and ANP release and blood pressure due to angiotensin and carbachol, and central GABA release due to blood pressure changes. 784 11

Morphological and pharmacological evidence suggest that the dense GABAergic innervation of the supraoptic nucleus is important for regulating the electrical activity of vasopressin and oxytocin neurons. We have employed the technique of intracranial microdialysis to examine extracellular GABA concentrations in the supraoptic nucleus of the anaesthetized rat and questioned whether differences exist in the dynamics of GABA release between virgin and lactating rats, and if events during lactation or following blood pressure manipulation alter endogenous GABA levels in this nucleus. No significant differences were detected between virgin and lactating animals in either basal or 100 mM potassium ion-evoked GABA release. The inclusion of the GABA uptake blocker nipecotic acid (0.5 mM) into the dialysate resulted in a six- to eight-fold increase (P < 0.01) in GABA outflow in both groups of animals. In lactating rats, GABA outflow measured at 4 min intervals was not altered during a 60 min period of suckling by a full litter of pups and no significant change in GABA outflow was detected in relation to individual milk ejections. In virgin rats, removal of 1.5-2 ml of blood resulted in a 30-60 mmHg fall in blood pressure and a non-significant decline in GABA outflow. Replacement of blood resulted in an abrupt 50 mmHg increase in blood pressure and a significant 22% increase in GABA outflow (P < 0.01), but no change in aspartate or methionine concentrations. Repeated intravenous injections of the alpha-adrenoceptor agonist, metaraminol, similarly evoked approximately 50 mmHg increments in blood pressure and a 26% increase in GABA outflow (P < 0.05). Electrical stimulation of the diagonal band of Broca for 10 min produced a two-fold increase in GABA outflow from the supraoptic nucleus (P < 0.05). These results show that the overall profile of basal and potassium-stimulated GABA concentrations in the supraoptic nucleus is not substantially different between lactating and virgin rats. In lactating animals we have found that GABA levels are not altered in response to suckling or at the time of high-frequency firing by oxytocin neurons to induce milk ejection. In contrast, our data further support the hypothesis that GABA inputs to supraoptic neurons are part of a baroreceptor reflex, relaying through the diagonal band of Broca, to signal periods of acute hypertension and inhibit the firing of vasopressin neurons. Such observations suggest the physiological importance of GABA inputs to the supraoptic nuclei and indicate that GABA may be used in a stimulus-specific manner to influence the activity of magnocellular neurons.
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PMID:Extracellular GABA concentrations in rat supraoptic nucleus during lactation and following haemodynamic changes: an in vivo microdialysis study. 789 64

Although the hypothalamus is generally regarded to have low levels of glutamate receptors, anatomical and physiological studies have provided consistent evidence implicating glutamate as a potential transmitter for the control of neuroendocrine cell activity. To clarify the extent of the contribution of synapses utilizing glutamate for control of vasopressin/oxytocin neuroendocrine cells, we mapped the density and location of glutamate immunoreactive terminals in the supraoptic nucleus and surrounding hypothalamus. Colloidal gold particle densities in presynaptic terminals were measured from electron micrographs of: (1) the magnocellular neuroendocrine cell perikarya (main body of the supraoptic nucleus), (2) the dendritic field of the magnocellular neuroendocrine cells (ventral dendritic neuropil) and (3) the hypothalamic perinuclear zone dorsal to the supraoptic nucleus. In addition, serial sections were stained, alternatively, for glutamate or GABA to determine glutamate staining in GABA cells. Terminals with high glutamate immunoreactivity were clearly distinguished from the glutamate precursor staining found in GABA terminals and were abundant at all rostral-caudal levels within each region. The number of glutamate terminals identified in each region was similar but represented a very high proportion of all terminals in the ventral dendritic neuropil (38%) vs. the main body of the supraoptic nucleus and the perinuclear zone (20-22%). The regional variation in the relative proportion of glutamate terminals was determined largely by differences in the number of non-glutamate terminals within each region. Glutamate and GABA terminals together accounted for over two-thirds of the innervation of vasopressin/oxytocin neuroendocrine cells. No systematic relationship was observed between excitatory and inhibitory inputs on the same cell. These results suggest that glutamate is the predominant excitatory transmitter used for control of vasopressin/oxytocin cells. The relative contribution of glutamate neurotransmission to a particular region will depend, in part, on the number and type of competing non-glutamate terminals.
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PMID:Quantitative mapping of glutamate presynaptic terminals in the supraoptic nucleus and surrounding hypothalamus. 809 74

The circadian timing system imposes a temporal organization on physiological processes and behavior. The two major nuclei of the system are the intergeniculate leaflet (IGL) of the lateral geniculate complex and the suprachiasmatic nucleus (SCN) of the hypothalamus. In this study, we demonstrate that neurons of both nuclei colocalize GABA with peptides. In the IGL, GABA is colocalized with neuropeptide Y in neurons projecting to the SCN and with enkephalin in neurons projecting to the contralateral IGL. In the SCN, GABA is colocalized with vasopressin and vasoactive intestinal polypeptide. All, or nearly all, of the neurons in the IGL and SCN are GABA-producing. Thus, GABA should be considered the principal neurotransmitter of the circadian system.
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PMID:GABA is the principal neurotransmitter of the circadian system. 809 23

Vasopressin-containing neurosecretory cells are partly regulated by GABAergic neurons present both at the hypothalamic and the pituitary level. In the present work, we compared GABA effects on vasopressin release from posterior pituitaries of Sprague-Dawley (SPD), Wistar (W), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Release of vasopressin was studied in vitro by placing neurointermediate lobes in perfusion chambers. It was stimulated twice by 50 mM KCl (S1 and S2) and the ratio between the first and the second stimulation was calculated (S2/S1). The basal and stimulated release of vasopressin was enhanced in the SHR. There was no difference in vasopressin content in the pituitary between the WKY and the SHR but the levels were lower compared to the SPD rat. Muscimol, a GABA-A receptor agonist, was added during S2. Muscimol inhibited in a dose-dependent manner the stimulated release of vasopressin, with an ED50 about 3 microM. The effect of muscimol was not statistically different between the strains expressed in ratios. The actual inhibition was apparently greater in the SHR, as both basal and stimulated vasopressin release was larger.
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PMID:GABA-A agonist muscimol inhibits stimulated vasopressin release in the posterior pituitary of Sprague-Dawley, Wistar, Wistar-Kyoto and spontaneously hypertensive rats. 811 20

1. Previous electrophysiological studies on rat hypothalamic supraoptic nucleus neurones have demonstrated that both the activation of peripheral baroreceptors (induced by a brief rise in arterial pressure consequent to an intravenous injection of an alpha-adrenergic agonist, metaraminol) and electrical stimulation in the diagonal band of Broca evokes a GABA-mediated postsynaptic inhibition which selectively involves the phasic-firing (putative vasopressin-secreting) neuronal population. Although baroreceptor-triggered inhibitions are abolished after diagonal band lesions, anatomical data support the hypothesis that the GABAergic neurones mediating both the baroreflex and electrically induced inhibitions are not located in the diagonal band, but rather in the lateral hypothalamus adjacent to the supraoptic nucleus. To determine the validity of this hypothesis, excitotoxic lesions were placed in the lateral hypothalamus and their effects on both baroreceptor- and diagonal band-evoked inhibitions were evaluated. 2. Male Long-Evans rats were initially anaesthetized with intraperitoneal pentobarbitone, stereotaxically injected with an excitotoxin (ibotenic acid) or vehicle into the lateral hypothalamus on the left side and allowed to recover. Three or more days later, animals were again anaesthetized with pentobarbitone and the ventral surface of their hypothalamus was exposed for electrophysiological recording of neurones in the left supraoptic nucleus. In all injected animals, extracellular recordings from antidromically identified, phasically firing supraoptic neurones were evaluated for their response to activation of peripheral baroreceptors and to electrical stimulation in the diagonal band. 3. Increases in arterial pressure sufficient to activate peripheral baroreceptors were achieved by intravenous bolus infusions of metaraminol (10 micrograms/10 microliters). In vehicle control animals (n = 6), the activity of 34/39 neurones was inhibited by baroreceptor activation. In lesion control animals (n = 13) similar inhibitions were observed from 60/65 neurones. In the lateral hypothalamic lesioned group (n = 7), the activity of only 12/34 neurones were inhibited by similar elevations in blood pressure. 4. Ibotenic acid lesions in the lateral hypothalamus also disrupted the responsiveness of supraoptic neurones to electrical stimulation in the diagonal band. Whereas diagonal band stimulation in vehicle control and lesion control rats reduced the excitability in 7/9 cells and 15/19 cells respectively, only 1/7 cells responded in the lesioned animals. 5. Lesions having a significant effect on the responsiveness of vasopressin-secreting neurones to baroreceptor activation extended laterally towards the nucleus of the lateral olfactory tract, dorsally into the striatum and medially to the fornix.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lateral hypothalamic lesions alter baroreceptor-evoked inhibition of rat supraoptic vasopressin neurones. 830 54

Suprachiasmatic nuclei (SCN) from hypothalami of postnatal rats were maintained for 18-39 days in vitro as organotypic slice explants. Neuronal subtypes containing vasopressin (VP), vasoactive intestinal polypeptide (VIP), gastrin releasing hormone (GRP), and GABA were immunocytochemically identifiable in these cultures. In situ hybridization histochemistry was compatible with these SCN slice explant cultures, and mRNA encoding for VP was detected bilaterally within these nuclei. After 18 days in vitro, both VP mRNA and VP immunoreactivity increased from levels present on postnatal days 4 (the earliest age from which the explanted tissue was derived) to levels typical of adult SCNs. In contrast, the GRP expression remained low, characteristic of early postnatal animals and far lower than adult levels. This suggests that the developmental cues or programs necessary for enhanced VP expression are maintained in these cultures, while those affecting GRP expression are absent or inhibited. VIP-containing neurons were numerous in the cultures. Culture slices appeared healthy, and similar numbers and distributions of identifiable neurons within the SCN were observed, whether or not the slices were grown in the presence of serum. EM analysis revealed that the SCN in vitro is composed of tightly packed neurons, processes, and abundant synapses containing both clear and dense core vesicles, closely resembling the SCN in vivo. Vasopressinergic neuronal somata contained extensive Golgi systems and labeled secretory granules, the latter organelle being present also within processes and synaptic terminals. GABA-immunopositive processes and synaptic profiles were abundant, with labeling occurring particularly over secretory vesicles and mitochondria. This slice culture system effectively maintained much of the intrinsic organization and cellular components of the SCN for long periods in vitro and should be an excellent model system for studying the intrinsic molecular mechanisms and extrinsic cues which regulate neuronal phenotype in this circadian pacemaker.
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PMID:Characterization of the suprachiasmatic nucleus in organotypic slice explant cultures. 835 7

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