Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The release of the hormones oxytocin (OT) and vasopressin (VP) into the circulation is dictated by the electrical activity of hypothalamic magnocellular neurosecretory cells (MNCs). In the paraventricular nucleus of the hypothalamus (PVN), MNC neuronal activity is exquisitely sensitive to changes in input from inhibitory GABAergic synapses. To explore the hypothesis that efficacy at these synapses is dictated by the rate at which a given synapse is activated, we obtained whole-cell recordings from MNCs in postnatal day 21-27 male Sprague Dawley rat brain slices. IPSCs were elicited by electrically stimulating GABAergic projections from either the suprachiasmatic nucleus or putative interneuron populations immediately ventral to the fornix at 5, 10, 20, and 50 Hz. Short-term plasticity was observed at 88% of the synapses tested. Of this group, synaptic depression was observed in 58%, and synaptic facilitation was observed in 41%. Identification of cells using a combined electrophysiological and immunohistochemical approach revealed a strong correlation between cell phenotype and the nature of the plasticity. Short-term facilitation was observed preferentially in OT cells (86%), whereas short-term depression was predominant in VP neurons (69%). We next examined the effects of dopamine, which increases MNC excitability, on short-term plasticity. Activation of presynaptic D(4) receptors decreased the frequency of miniature IPSCs and prevented the development of synaptic depression at higher rates of activity. Synaptic facilitation, however, was unaffected by dopamine. These findings demonstrate that, by lowering GABA release probability, dopamine confers high-pass filtering properties to the majority of inhibitory synapses onto MNCs in PVN.
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PMID:Dopamine modulates use-dependent plasticity of inhibitory synapses. 1517 85

The present mini review focuses on stress-induced alterations of the electrical and secretory activity of vasopressin (AVP) and oxytocin (OXT) neurones originating within the supraoptic nucleus (SON) and constituting the hypothalamo-neurohypophysial system (HNS) in the male rat. Previously, it was thought that SON neurones are predominantly activated by osmotic and reproductive stimuli. However, recent findings also suggest a selective activation of AVP and/or OXT neurones in response to specific stressors. Inhibitory amino acids seem to participate at the level of the SON in the control of HNS activity during stress. Taurine, probably of glial origin, selectively inhibits the secretory activity of AVP neurones. In contrast, GABA, probably of neuronal origin, interferes with the release of OXT both from axon terminals into blood and from somata/dendrites into the extracellular fluid of the SON. Depending upon whether a defined stressor triggers taurine and/or GABA release within the SON the secretion of AVP and/or OXT from HNS neurones will be inhibited. These observations shed new light on the neurone-neurone and glial-neurone interactions that ensure an appropriate neuroendocrine stress response.
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PMID:The activity of the hypothalamo-neurohypophysial system in response to acute stressor exposure: neuroendocrine and electrophysiological observations. 1551 52

It is now well accepted that the sympathetic nervous system responds to specific afferent stimuli in a unique non-uniform fashion. The means by which the brain transforms the signals from a single type of receptor into an appropriate differential sympathetic output is discussed in this brief review. The detection of and response to venous filling are used for illustration. An expansion of blood volume has been shown in a number of species to increase heart rate reflexly via sympathetic nerves and this effect is primarily an action of volume receptors at the venous-atrial junctions of the heart. Stimulation of these volume receptors also leads to an inhibition of renal sympathetic nerve activity. Thus the reflex response to an increase in plasma volume consists of a distinctive unique pattern of sympathetic activity to maintain fluid balance. This reflex is dependent on neurones in the paraventricular nucleus (PVN). Neurones in the PVN show early gene activation on stimulation of atrial receptors, and a similar differential pattern of cardiac sympathetic excitation and renal inhibition can be evoked by activating PVN neurones. Cardiac atrial afferents selectively cause a PVN GABA neurone-induced inhibition within the PVN of PVN spinally projecting vasopressin-containing neurones that project to renal sympathetic neurones. A lesion of these spinally projecting neurones abolishes the reflex. With regard to the cardiac sympathetics, there is a population of PVN spinally projecting neurones that selectively increase heart rate by the release of oxytocin, a peptide pathway that has no action on renal sympathetic outflow. In heart failure the atrial reflex becomes blunted, and evidence is emerging that there is a downregulation of nitric oxide synthesis and reduced GABA activity in the PVN. How this might give rise to increased sympathetic activity associated with heart failure is briefly discussed.
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PMID:A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney. 1560 10

The successful treatment of Cushing syndrome depends on specific therapy directed against the etiology of hypercortisolism. In addition to surgical procedures, various drugs have been employed in the management of this difficult disease. Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation. The most exciting news, however, in the pharmacologic approach to Cushing syndrome refers to the adrenal corticotropin (adrenocorticotropic hormone; ACTH)-independent forms, in which aberrant adrenal receptors, through the binding of their respective ligands, could lead to chronic cortisol overproduction. They include receptors for gastric inhibitory peptide (GIP), beta-adrenergic agonists, luteinizing hormone (LH)/human chorionic gonadotropin, serotonin (5-HT(4) receptor), vasopressin (V(1) receptor), and angiotensin II (AT(1) receptor). In GIP-dependent Cushing syndrome, the most frequent subtype of ACTH-independent macronodular adrenal hyperplasia associated with the presence of aberrant adrenocortical hormone receptors described so far, octreotide administration before each meal showed clinical efficacy only in the first few months, probably because of somatostatin receptor downregulation in GIP-secreting cells. Long-term medical treatments with propranolol and the gonadotropin-releasing hormone analog leuprorelin (leuprolide acetate) were effective in patients with catecholamine-dependent and LH-dependent Cushing syndrome, respectively. The oral vasopressin V(1) receptor antagonist OPC-21268 and the angiotensin II (AT(1)) receptor antagonist candesartan cilexetil were also able to decrease cortisol levels during the few days of administration of the drugs in patients with specific receptor abnormalities. These adrenal forms of Cushing syndrome are rare, and clinical data are scarce. Moreover, the real clinical significance of aberrant hormone receptors is still under investigation, as is the possibility of avoiding surgery by pharmacologic manipulation. Patients in whom these intriguing syndromes are suspected require detailed investigation protocols, which should be carried out in specialized centers. While awaiting further developments, the use of traditional medical treatment at the adrenal level with adrenal steroid inhibitors is still valuable in several instances.
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PMID:Pharmacologic management of Cushing syndrome : new targets for therapy. 1578 46

GABA is one of the key neurotransmitters that regulate the firing activity of neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. In the present study, we used immunohistochemical techniques to study the distribution and subcellular localisation of metabotropic GABA(B) receptors in magnocellular neurones in the SON and PVN. Robust GABA(B) receptor immunoreactivity (GABA(B)R; both subunit 1 and subunit 2 of the heterodimer), was observed in the SON and PVN. At the light microcope level, GABA(B)R immonoreactivity displayed a clustered pattern localised both intracytoplasmically and at the plasma membrane. Densitometry analysis indicated that GABA(B)R immunoreactivity was significantly more intense in vasopressin cells than in oxytocin cells, both in male, virgin female and lactating rats, and was denser in males than in virgin females. Light and electron microscope studies indicated that cytoplasmic GABA(B)R was localised in various organelles, including the Golgi, early endosomes and lysosomes, suggesting the cycling of the receptor within the endocytic and trafficking pathways. Some smaller clusters at the level of the cell plasma membrane were apposed to glutamic acid decarboxylase 67 immunoreactive boutons, and appeared to be colocalised with gephyrin, a constituent protein of the postsynaptic density at inhibitory synapses. The presence of GABA(B)R immunoreactivity at synaptic and extrasynaptic sites was supported by electron microscopy. These results provide anatomical evidence for the expression of postsynaptic GABA(B) receptors in magnocellular neurosecretory cells.
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PMID:Expression of GABAB receptors in magnocellular neurosecretory cells of male, virgin female and lactating rats. 1594 59

A number of neurohumoral processes are activated in heart failure, including an increase in the plasma concentration of norepinephrine. Few studies have been performed to examine the role of the central nervous system in the activation of sympathetic outflow during heart failure (HF). In this paper I review these limited studies, with particular emphasis on examining the role of the paraventricular nucleus (PVN) in the exaggerated sympathetic outflow commonly observed in heart failure. The conclusion is that heart failure is associated with changes in specific areas in the brain and that alterations in the activation of neurons in the PVN are likely related to abnormalities in vasopressin production, blood volume regulation, and sympathoexcitation observed in the heart failure state. Furthermore, neuronal nitric oxide within the PVN that is involved in mediating sympathetic outflow via a GABA mechanism from the PVN may be deficient in inhibiting overall sympathetic outflow leading to the exaggerated sympathetic outflow commonly observed in heart failure.
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PMID:Role of paraventricular nucleus in mediating sympathetic outflow in heart failure. 1622 17

We recently showed that central injections of alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits oxytocin cells and reduces peripheral release of oxytocin, but induces oxytocin release from dendrites. Dendritic oxytocin release can be triggered by agents that mobilize intracellular calcium. Oxytocin, like alpha-MSH, mobilizes intracellular calcium stores in oxytocin cells and triggers presynaptic inhibition of afferent inputs that is mediated by cannabinoids. We hypothesized that this mechanism might underlie the inhibitory effects of alpha-MSH. To test this, we recorded extracellularly from identified oxytocin and vasopressin cells in the anesthetized rat supraoptic nucleus (SON). Retrodialysis of a CB1 cannabinoid receptor antagonist to the SON blocked the inhibitory effects of intracerebroventricular injections of alpha-MSH on the spontaneous activity of oxytocin cells. We then monitored synaptically mediated responses of SON cells to stimulation of the organum vasculosum of the lamina terminalis (OVLT); this evoked a mixed response comprising an inhibitory component mediated by GABA and an excitatory component mediated by glutamate, as identified by the effects of bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione applied to the SON by retrodialysis. Application of CB1 receptor agonists to the SON attenuated the excitatory effects of OVLT stimulation in both oxytocin and vasopressin cells, whereas alpha-MSH attenuated the responses of oxytocin cells only. Thus alpha-MSH can act as a "switch"; it triggers oxytocin release centrally, but at the same time through initiating endocannabinoid production in oxytocin cells inhibits their electrical activity and hence, peripheral secretion.
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PMID:Presynaptic actions of endocannabinoids mediate alpha-MSH-induced inhibition of oxytocin cells. 1626 71

The magnocellular neurons of the hypothalamic supraoptic nucleus (SON) synthesize and secrete oxytocin (OXT) and vasopressin (AVP) from their dendrites. These peptides, and several other neurotransmitters, have been shown to modulate afferent glutamatergic neurotransmission in the SON. The neuropeptide, galanin (GAL) is also localized in SON magnocellular neurons and in afferent fibers in the nucleus. We show that GAL dose-dependently reduces evoked excitatory postsynaptic currents (eEPSCs), alters paired pulse ratio and decreases mEPSC frequency, but not amplitude or decay kinetics in both OXT and AVP neurons. GAL therefore modulates excitatory neurotransmission at a likely presynaptic receptor. Neither OXT/AVP, GABA(B) nor cannabinoid antagonists blocked this effect. A GAL2/3 agonist mimicked GAL's action while GAL1 antagonist did not block GAL's effect, suggesting that GAL2/3 receptors mediate the presynaptic effect. In nondehydrated rats GAL causes a small postsynaptic response, as assessed by input resistance measurements. When the rats were water deprived for 2 days the presynaptic response to GAL was unaltered; however, the postsynaptic decrease in input resistance and hyperpolarization was increased, an effect consistent with a previously described increase in GAL1 receptor expression in dehydration. A GAL1 receptor antagonist blocked the postsynaptic effects. Last, when a train of eEPSCs was elicited, GAL was found to inhibit the earlier events in a train but not the latter. This indicates that GAL may modulate a single synaptic event more effectively than trains of synaptic inputs, thereby acting as a high-pass filter.
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PMID:Galanin modulates neuronal and synaptic properties in the rat supraoptic nucleus in a use and state dependent manner. 1661 41

In addition to mediating conventional quantal synaptic transmission (also known as phasic inhibition), gamma-aminobutyric acidA (GABAA) receptors have been recently shown to underlie a slower, persistent form of inhibition (tonic inhibition). Using patch-clamp electrophysiology and immunohistochemistry, we addressed here whether a GABAA receptor-mediated tonic inhibition is present in supraoptic nucleus (SON) neurosecretory neurons; identified key modulatory mechanisms, including the role of glia; and determined its functional role in controlling SON neuronal excitability. Besides blocking GABAA-mediated inhibitory postsynaptic currents, the GABAA receptor blockers bicuculline and picrotoxin caused an outward shift in the holding current (I(tonic)), both in oxytocin and vasopressin neurons. Conversely, the high-affinity antagonist gabazine selectively blocked inhibitory postsynaptic currents. Under basal conditions, I(tonic) was independent on the degree of synaptic activity but was strongly modulated by the activity GABA transporters (GATs), mostly the GAT3 isoform, found here to be localized in SON glial cells/processes. Extracellular activation of GABAergic afferents evoked a small gabazine-insensitive, bicuculline-sensitive current, which was enhanced by GAT blockade. These results suggest that I(tonic) may be activated by spillover of GABA during conditions of strong and/or synchronous synaptic activity. Blockade of I(tonic) increased input resistance, induced membrane depolarization and firing activity, and enhanced the input-output function of SON neurons. In summary, our results indicate that GABAA receptors, possibly of different molecular configuration and subcellular distribution, mediate synaptic and tonic inhibition in SON neurons. The latter inhibitory modality plays a major role in modulating SON neuronal excitability, and its efficacy is modulated by the activity of glial GATs.
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PMID:Characterization of a novel tonic gamma-aminobutyric acidA receptor-mediated inhibition in magnocellular neurosecretory neurons and its modulation by glia. 1667 19

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each of which is dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock producing a coherent output that is able to time all the different daily changes in behavior and physiology. We investigated which anatomical connections and neurotransmitters are used by the biological clock to control the daily release pattern of a number of hormones. The picture that emerged shows projections contacting target neurons in the medial hypothalamus surrounding the SCN. The activity of these pre-autonomic and neuro-endocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together our data indicate that, with regard to the timing of their main release period within the light-dark (LD) cycle, at least 4 subpopulations of SCN neurons should be discerned. The different subgroups do not necessarily follow the phenotypic differences among SCN neurons. Thus, different subgroups can be found within neuron populations containing the same neurotransmitter. Remarkably, a similar distinction of 4 differentially timed subpopulations of SCN neurons was recently also discovered in experiments determining the temporal patterns of rhythmicity in individual SCN neurons by way of the electrophysiology or clock gene expression. Moreover, the specialization of the SCN may go as far as a single body structure; i.e., the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal.
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PMID:A network of (autonomic) clock outputs. 1668 94


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