Regulation Of Vasopressin Release Research Articles

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis.

Located in the midline anterior wall of the third cerebral ventricle (i.e. the lamina terminalis), the median preoptic nucleus (MnPO) receives a unique set of afferent neural inputs from fore-, mid- and hindbrain. These afferent connections enable it to receive neural signals related to several important aspects of homeostasis. Included in these afferent projections are (i) neural inputs from two adjacent circumventricular organs, the subfornical organ and organum vasculosum laminae terminalis, that respond to hypertonicity, circulating angiotensin II or other humoural factors, (ii) signals from cutaneous warm and cold receptors that are relayed to MnPO, respectively, via different subnuclei in the lateral parabrachial nucleus and (iii) input from the medulla associated with baroreceptor and vagal afferents. These afferent signals reach appropriate neurones within the MnPO that enable relevant neural outputs, both excitatory and inhibitory, to be activated or inhibited. The efferent neural pathways that proceed from the MnPO terminate on (i) neuroendocrine cells in the hypothalamic supraoptic and paraventricular nuclei to regulate vasopressin release, while polysynaptic pathways from MnPO to cortical sites may drive thirst and water intake, (ii) thermoregulatory pathways to the dorsomedial hypothalamic nucleus and medullary raphé to regulate shivering, brown adipose tissue and skin vasoconstriction, (iii) parvocellular neurones in the hypothalamic paraventricular nucleus that drive autonomic pathways influencing cardiovascular function. As well, (iv) other efferent pathways from the MnPO to sites in the ventrolateral pre-optic nucleus, perifornical region of the lateral hypothalamic area and midbrain influence sleep mechanisms.

Role of purinergic P2Y1 receptors in regulation of vasopressin and oxytocin secretion

Pharmacological studies demonstrated that ATP elevates intracellular calcium ([Ca(2+)](i)) in supraoptic nucleus (SON) neurons primarily by activation of P2X2 and P2Y1 purinergic receptors [P2Y1R]. The current studies provide evidence for the presence of P2Y1R protein in SON neurons, evidence that activation of these P2Y1Rs induces an increase in [Ca(2+)](i) from both intracellular stores and Ca(2+) influx, and functional evidence that activation of P2Y1Rs induces vasopressin (VP) and oxytocin (OT) hormone release. Pretreatment of Fura-2 AM-loaded explants of the hypothalamo-neurohypophyseal system (HNS) with thapsigargin (TG) significantly (approximately 80%) reduced the increase in [Ca(2+)](i) induced by the P2Y1R-specific agonist, 2-methylthio-ADP (2-MeSADP). In contrast, the increase in [Ca(2+)](i) was slightly (approximately 20%) decreased in calcium-free medium. The calcium response to 2-MeSADP was completely blocked by the P2Y1R-specific antagonist, MRS2179 or by a combination of TG pretreatment and calcium-free medium. It was absent in P2Y1R knockout mice (P2Y1R(-/-)). 2-MeSADP significantly increased VP and OT release from perifused rat and wild-type mouse HNS explants compared with control. MRS2179 prevented this response in wild-type mouse, but it did not prevent ATP-induced hormone release from rat explants. 2-MeSADP did not induce hormone release from P2Y1R(-/-) explants. These findings support a potential role for P2Y1Rs in regulation of VP and OT release. The finding that P2Y1R activation induces a small Ca(2+) influx suggests that P2Y1Rs may regulate VP release by modifying ion channels such as stretch-inactivated cation channels.

Neuroendocrine regulatory peptide-1 and -2: novel bioactive peptides processed from VGF.

Neuroendocrine regulatory peptides (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. The amino acid length of human NERP-1 is 26, and that of rat NERP-1 is 25. Human and rat NERP-2 are both 38 amino acid peptides. NERPs colocalize with vasopressin in the storage granules of the paraventricular and supraoptic nuclei in the hypothalamus of both rats and humans. Administration of NERPs suppresses hypertonic saline- or angiotensin II-induced vasopressin release from the hypothalamus and pituitary. Thus, VGF is a precursor of multiple bioactive peptides with diverse neuroendocrine functions, and NERPs are novel hypothalamic peptides involved in the control of body fluid homeostasis by regulating vasopressin release.

Altered vasopressin response to metoclopramide in multiple system atrophy: evidence of a cholinergic defect in the hypothalamus.

Multiple system atrophy (MSA) is a heterogeneous group of central neurological degenerations often associated with diffuse deterioration of the hypothalamic cholinergic neurons. In the hypothesis of an altered cholinergic regulation of vasopressin release, we evaluated vasopressin response to metoclopramide (20 mg i.v.), a cholinomimetic agonist, in 12 MSA patients. In the same patients the hemodynamic and osmolal control of vasopressin was also evaluated. We found that MSA patients had significantly lower basal plasma vasopressin values and higher plasma osmolality than control subjects. However, they displayed a normal vasopressin response to osmotic stimulation. During head-up tilting, orthostatic hypotension occurred in all patients, and the vasopressin response to hypotension was severely blunted in 5 of 12 patients, thus demonstrating the presence of a lesion of the afferent noradrenergic pathways. Metoclopramide increased vasopressin in control subjects, whereas MSA patients did not display any increase in vasopressin. These results clearly indicate that cholinergic neurons that regulate vasopressin release are damaged in MSA. Such an alteration may be dissociated from the lesion of the afferent noradrenergic pathways. As a consequence of the altered vasopressin release, MSA patients show lower plasma vasopressin levels with consequent propensity to dehydration and hypovolemia, which may further aggravate their hypotension.

Morphological Substrate of the Catecholaminergic Input of the Vasopressin Neuronal System in Humans

It has been postulated that the stress response is associated with water balance via regulating vasopressin release. Nausea, surgical stress and insulin-induced hypoglycaemia were shown to stimulate vasopressin secretion in humans. Increased vasopressin release in turn induces water resorption through the kidneys. Although the mechanism of the stress-mediated vasopressin release is not entirely understood, it is generally accepted that catecholamines play a crucial role in influencing water balance by modulating the secretion of vasopressin. However, the morphological substrate of this modulation has not yet been established. The present study utilised double-label immunohistochemistry to reveal putative juxtapositions between tyrosine hydroxylase (TH)-immunoreactive (IR) catecholaminergic system and the vasopressin systems in the human hypothalamus. In the paraventricular and supraoptic nuclei, numerous vasopressin-IR neurones received TH-IR axon varicosities. Analysis of these juxtapositions with high magnification combined with oil immersion did not reveal any gaps between the contacted elements. In conclusion, the intimate associations between the TH-IR and vasopressin-IR elements may be functional synapses and may represent the morphological basis of vasopressin release modulated by stressors. Because certain vasopressin-IR perikarya receive no detectable TH innervations, it is possible that additional mechanisms may participate in the stress-influenced vasopressin release.

Inhibitory effects of different galanin compounds and fragments on osmotically and histamine-induced enhanced vasopressin secretion in rats

The effects of rat, porcine and human galanin, and the human 1–16 and human 16–30 terminal galanin fragments on vasopressin secretion were studied in rat. The plasma vasopressin level was determined by radioimmunoassay (RIA). There were no changes in the basal vasopressin secretion after galanin administration. A significant increase in vasopressin concentration was detected following 2.5% NaCl or histamine administration. I.c.v. injected rat, porcine or human galanin or the 1–16 N-terminal galanin fragment prevented the plasma vasopressin level enhancement. Following the i.v. administration of rat galanin or the i.c.v. injected 16–30 C-terminal galanin fragment, the vasopressin concentration did not return to the normal level. Administration of the galanin antagonist galantid (M15) i.c.v. before the rat galanin i.c.v. injection prevented the inhibitory effect on the increased plasma vasopressin level following 2.5% NaCl solution or histamine administration. The results indicate that there is no significant difference in the inhibitory effect of rat, porcine or human galanin or the 1–16 galanin fragment on the enhanced plasma vasopressin secretion induced by hyperosmosis or histamine administration. Our findings suggest that galanin, as a peptide modulator, is physiologically involved in the regulation of vasopressin release following different forms of stimulation: an osmotic response or histamine administration.

Vasopresin and human hypertension.

1. Two clinical studies are reported which investigate: (1) the regulation of vasopressin release in moderate hypertensive subjects not under treatment compared to normotensives and, (2) the effects of antihypertensive treatment on vasopressin and on its osmoregulation in moderate hypertensives. 2. In the first study two stimuli facilitating vasopressin release (active upright position and hypertonic saline infusion) and a stimulus inhibiting vasopressin release (hypotonic saline infusion) have been applied to 13 moderate essential hypertensives and 8 control normotensives. In the second study, limited to hypertensives, the effects on plasma vasopressin and other plasma and urine variables, of either acute (by clonidine, n = 6 or by sodium nitroprusside, n = 6) or chronic (antihypertensive treatment for 1 month, n = 8) blood pressure lowering, before and after the i.v. administration of a hypertonic NaCl solution, were investigated. 3. Baseline plasma vasopressin was not different in hypertensive and in normotensive subjects. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels with no difference between the two groups. Acute, but not chronic, lowering of blood pressure increased plasma vasopressin from 1.6 +/- 0.63 to 3.4 +/- 0.7 pg/mL (p < 0.05); administration of hypertonic saline further increased vasopressin to 10.8 +/- 2.22 (p < 0.01) in the acute and to 6.0 +/- 1.03 pg/mL (p < 0.01) in the chronic study. 4. No significant alterations of the regulation of vasopressin have been found in moderate, uncomplicated hypertension. Moreover, acute lowering of blood pressure facilitated the release of vasopressin and its osmoregulation while a chronic antihypertensive treatment did not interfere with a normal control of vasopressin secretion.

Role of ghrelin in the regulation of vasopressin release in conscious rats.

GH secretagogue (GHS) is a small, synthetic compound that has the potential to stimulate GH release via its specific receptors (GHS-R). Ghrelin is a novel 28-amino acid peptide recently isolated from human and rat stomach, and it is thought to be the endogenous ligand for GHS-R. Ghrelin has a variety of physiological functions such as the stimulation of GH release or the increase of food intake by activating NPY neurons. In the present study, we investigated the effects of ghrelin on AVP release in conscious rats. Intracerebroventricular (icv) administration of ghrelin increased the plasma AVP concentration in a dose-dependent manner (1-1000 pmol/rat), and its effect was observed as late as 60 min after the administration. Icv injection of ghrelin caused no significant change in plasma osmolality, plasma volume, or arterial blood pressure. Iv administration of ghrelin (10 nmol/rat) also increased the plasma AVP concentration, which was accompanied by a significant decrease in arterial blood pressure. Pretreatment with antiserum against NPY significantly reduced the plasma AVP increase induced by icv administration of ghrelin. These results suggest that ghrelin plays a stimulatory role in AVP release, which is possibly mediated by NPY neurons.

Role of Ghrelin in the Regulation of Vasopressin Release in Conscious Rats

Role of Ghrelin in the Regulation of Vasopressin Release in Conscious Rats

Regulation of vasopressin release by ionotropic glutamate receptor agonists.

Immunocytochemistry, in situ hybridization, and electrophysiological techniques have demonstrated the presence of excitatory amino acid (EAA) receptors in the supraoptic nuclei(1–4). A role for EAA regulation of vasopressin (VP) release is suggested by the ability of the non-specific EAA antagonist, kynureic acid, to inhibit osmotically stimulated VP release from explants of the hypothalamo-neurohypophyseal system (HNS)(5). In addition, both N-methyl-D-aspartate (NMDA) receptor antagonists (AP5 and MK801) and the non-NMDA receptor antagonist, DNQX, applied independently inhibit osmotically stimulated VP release implicating the importance of both classes of glutamate receptors in the regulation of VP release.KeywordsGlutamate ReceptorExcitatory Amino AcidKainic AcidKynureic AcidReceptor DesensitizationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Gonadal steroid modulation of vasopressin secretion in response to osmotic stimulation.

As deficiencies in osmotic stimulation of vasopressin (VP) messenger RNA (mRNA) content in castrated rats have been reported, experiments were performed to determine whether castration altered osmotically stimulated VP release in vitro. Perifused explants of the hypothalamo-neurohypophyseal system were obtained from sham and gonadectomized male rats. There were no significant differences in VP release stimulated by a ramp increase in the osmolality of the culture medium between the two groups. As testosterone was undetectable in the perifusion medium, the effect of addition of testosterone on osmotically stimulated VP release was evaluated. Testosterone (3 ng/ml) and its metabolites, estradiol (50 pg/ml) and dihydrotestosterone (DHT; 3 ng/ml), inhibited osmotically stimulated VP release in hypothalamo-neurohypophyseal system explants. The osmotically induced increase in VP mRNA content was also inhibited by testosterone and estradiol, but not by DHT. Neither estradiol nor DHT affected stimulus-secretion coupling of hormone secretion, because they did not inhibit KCl (25 mM)-stimulated VP release. BSA conjugates of estradiol (200 nM) and DHT (10 mM) also inhibited osmotically stimulated VP release, and VP mRNA content was inhibited by BSA-estradiol, but not by BSA-DHT, suggesting nongenomic actions of the steroids. The differential effects of estradiol and DHT on VP mRNA imply distinct actions for these steroids, and the DHT mechanism uncouples regulation of VP release from VP mRNA content.

Gadolinium Uncouples Mechanical Detection and Osmoreceptor Potential in Supraoptic Neurons

Stretch-sensitive ion channels are ubiquitous, yet evidence of their role in mechanotransduction remains scarce. The presence of stretch-inactivated cation channels in supraoptic neurons is consistent with the osmoreceptor potentials regulating vasopressin release. However, whether osmosensitivity depends on mechanical gating and ion flux through stretch-inactivated channels is unknown. Here we report that changes in channel open probability associated either with modification of pipette pressure or with external osmolality selectively result from variations in closed time. While channel mechanosensitivity and osmotically evoked changes in cell volume are not affected by gadolinium, similar concentrations of the lanthanide inhibit cation permeation through the single channels and macroscopic osmoreceptor potentials. Mechanotransduction through stretch-inactivated channels is therefore necessary for osmoreception in supraoptic neurons.

Cardiovascular Effects of Endothelin Injected into Brain Nuclei Regulating Vasopressin Release

Summary: We studied the cardiovascular effects produced by administration of endothelin-1 (ET-1) into brain nucleic known to affect vasopressin release. In urethane-anesthetized Sprague-Dawley rats, microinjection of ET-1 into the subfornical organ (SFO) resulted in a dose-dependent increase in arterial blood pressure and a decrease in heart rate. These effects were inhibited by previous administration of the ETA receptor antagonist BQ-123 or by intravenous administration of a vasopressin antagonist. In addition, microinjection of ET-1 into the SFO increased plasma levels of vasopressin. In contrast, in the paraventricular nucleus (PVN) of the hypothalamus microinjection of ET-1 evoked a dose-related bradycardia with inconsistent changes in blood pressure. Although the bradycardia was antagonized by intra-PVN administration of BQ-123, the vasopressin antagonist did not affect the changes in heart rate evoked by microinjection of this peptide into the PVN. Overall, these results indicate that the central cardiovascular effects of ET-1 result from activation of several mechanisms, including stimulation of brain centers regulating vasopressin release.

Cardiovascular Effects of Endothelin Injected into Brain Nuclei Regulating Vasopressin Release

We studied the cardiovascular effects produced by administration of endothelin-1 (ET-1) into brain nucleic known to affect vasopressin release. In urethane-anesthetized Sprague-Dawley rats, microinjection of ET-1 into the subfornical organ (SFO) resulted in a dose-dependent increase in arterial blood pressure and a decrease in heart rate. These effects were inhibited by previous administration of the ETA receptor antagonist BQ-123 or by intravenous administration of a vasopressin antagonist. In addition, microinjection of ET-1 into the SFO increased plasma levels of vasopressin. In contrast, in the paraventricular nucleus (PVN) of the hypothalamus microinjection of ET-1 evoked a dose-related bradycardia with inconsistent changes in blood pressure. Although the bradycardia was antagonized by intra-PVN administration of BQ-123, the vasopressin antagonist did not affect the changes in heart rate evoked by microinjection of this peptide into the PVN. Overall, these results indicate that the central cardiovascular effects of ET-1 result from activation of several mechanisms, including stimulation of brain centers regulating vasopressin release.

Effect of dopamine injection into the anteroventral third ventricular region and the paraventricular nucleus on vasopressin secretion in conscious rats.

To investigate the role of dopamine receptors situated in the paraventricular nucleus and the anteroventral third ventricular region in regulating vasopressin release, responses of plasma AVP and its controlling factors to injections of dopamine into these regions and the lateral cerebral ventricle were examined in conscious rats. The injections of 156 nmol (30 micrograms) dopamine into the cerebral ventricle produced transient rises in plasma AVP 5 min later. When the dose of dopamine was reduced to 26 nmol (5 micrograms), the increase in plasma AVP was not provoked any more. However, injections of 26 nmol dopamine into the paraventricular nucleus greatly augmented plasma AVP 5 and 15 min later. This dose of dopamine was without effect on plasma AVP when injected into the anteroventral third ventricular region, including the organum vasculosum lamina terminalis, median preoptic nucleus, medial preoptic area and the periventricular preoptic nucleus. These dopamine administrations in the cerebral ventricle, paraventricular nucleus and the anteroventral third ventricular region did not significantly change AVP-controlling factors such as plasma osmolality, sodium and arterial pressure. On the basis of these results, we conclude that dopamine receptors in the paraventricular nucleus may function to facilitate AVP secretion, whereas those in the anteroventral third ventricular region may not play an important role in the regulation of AVP release.

Regulation of vasopressin release in moderately severe essential hypertension

Vasopressin plasma concentrations have been measured in two groups of subjects, 13 moderate essential hypertensive patients without target organ damage and eight control normotensive subjects, before and after the assumption of the upright position, and intravenous infusions of hypotonic saline (0.45% NaCl, 0.25 ml kg-1 min-1 for 1 h) and hypertonic saline (100 mmol NaCl in 50 ml). Plasma vasopressin in recumbent baseline conditions was not significantly different in the two groups. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels, which were not significantly different between the two groups. Plasma renin activity increased in the upright position, was reduced by administration of hypotonic saline and unaffected by hypertonic saline, with no differences between the hypertensives and normotensives. After hypertonic saline, urinary flow rate and urinary sodium excretion in the hypertensive group increased to values significantly (p less than 0.05) higher than in normotensive subjects. In conclusion our study excludes significant alteration of vasopressin regulation in moderate uncomplicated hypertension. In hypertensives although the response of vasopressin to an osmotic load is preserved, the data suggest that the renal handling of the osmotic load may be altered.

Inhibition by Brain Natriuretic Peptide of Vasopressin Neurons in the Supraoptic Nucleus and Neurons in the Region of the Anteroventral Third Ventricle in Rat Hypothalamic Slice Preparations

Abstract It is not entirely clear whether or not atrial natriuretic peptide (ANP) directly inhibits vasopressin neurons in the supraoptic nucleus (SON) and paraventricular nucleus. Recently, a novel peptide, brain natriuretic peptide (BMP), which has been isolated from the brain, has been shown to have a similar action to ANP on the regulation of vasopressin release. Intracerebroventricular injection of both BNP and ANP inhibits stimulus-evoked increases of plasma vasopressin level. The present study was undertaken: 1) to investigate whether BNP affects the activity of neurons in the region of the anteroventral third ventricle (AV3V) and SON which are involved in the control of body fluid homeostasis and blood pressure regulation, 2) to reassess effects of ANP on SON neurons, and 3) to test whether BNP exerts its effects by mechanisms which are different from those of ANP. Extracellular recordings were made from 213 AV3V and 110 SON spontaneously firing neurons in the rat coronal hypothalamic slice preparation. Of the AV3V neurons tested, BNP inhibited 86 (40%) and excited 2 (1%) while 125 neurons remained unaffected. A dose-response relationship was obtained for 7 AV3V neurons at different BNP concentrations ranging from 10(-11) M to 10(-6) M; the firing rates of all 7 neurons decreased. The threshold concentration to evoke inhibitory responses was approximately 10(-10)M in the AV3V. When BNP and ANP were applied to the same neuron, most AV3V neurons which were inhibited by BNP were also inhibited by ANP and the neurons which were unaffected by BNP were also unaffected by ANP. Thus, these two peptides probably have a similar action on AV3V neurons. When BNP and angiotensin II were applied to a group of 60 neurons in the AV3V, most of the responsive neurons showed either inhibitory responses to BNP or excitatory responses to angiotensin II. Both BNP and ANP were applied to a group of 110 SON neurons: BNP (10 (-7) M) inhibited 52 (75%) of 69 phasic (putative vasopressin) neurons, while BNP affected none of the 41 non-phasic (putative oxytocin) neurons. By contrast, ANP inhibited only 20 (29%) of 69 phasic neurons tested but it also had no effect on 41 non-phasic neurons tested. Our results are consistent with the suggestion that BNP is involved in the regulation of vasopressin release by acting on SON neurons and AV3V neurons.

Arginine vasopressin and body fluid homeostasis in the fetal alcohol exposed rat

Studies involving fluid homeostasis were carried out in adult Long-Evans rats born to mothers given liquid diets containing 35% of the calories derived from ethanol and compared to offspring of dams given isocaloric liquid diets containing no ethanol. Plasma levels of arginine vasopressin (AVP), plasma and urine osmolality, and urine production were determined in water-sated and water-deprived offspring. In the water-sated condition, the group exposed to alcohol prenatally had plasma levels of AVP seven-fold above control levels. This increase was associated with a large increase in within-group variability. Water consumption was also significantly elevated in the group of fetal alcohol exposed (FAE) rats. Plasma and urine osmolality and urine production were similar to control levels. In the control animals, 24-hr of water deprivation produced the expected increase in AVP, in plasma and urine osmolality, and decrease in urine production. The FAE animals, however, showed parallel changes in plasma and urine osmolality and urine production with no significant change in AVP. Examination of basal glucose metabolic rates in the cerebral structures involved in fluid homeostasis revealed that despite the large increase in AVP levels in the FAE rats, only the neurohypophysis and supraoptic nuclei showed significant increases in activity. These data suggest that fetal alcohol exposure causes a long-term disruption in the central mechanisms regulating vasopressin release and fluid homeostatic responses.

Neuroanatomical and biochemical evidence for the involvement of the area postrema in the regulation of vasopressin release in rats

Studies were carried out in the rat to determine if the area postrema (AP), a medullary circumventricular organ, might be involved in the control of vasopression (VP) release, The data from this study demonstrate the existence of direct neural connections between the AP and the hypothalamic VPergic neurons of the supraoptic nucleus (SON) as showed by the retrograde tracer horseradish peroxidase (HRP). Labeled neurons were observed in the AP following HRP injections into the SON. In addition, rats with AP lesions showed an impaired abiility to conserve water and concentrate their urine in response to an hypertonic NaCl load. They, also, failed to maintain sodium retention and showed an attenuation of VP release during intracellular dehydration. These findings indicate that AP plays an important role in the regulation of VP release during changes in osmotic environment and suggest that this medullary circumventricular organ is a part of central circuitry subserving salt-water balance.

γ-Aminobutyric Acid Antagonists Stimulate Vasopressin Release from Organ-Cultured Hypothalamo-Neurohypophyseal Explants*

gamma-Aminobutyric acid (GABA) has been identified in axon terminals innervating neurons of the supraoptic nucleus and has been shown to inhibit the electrical activity of supraoptic neurons when applied iontophoretically. This study examines the effects of GABA and GABA antagonists on vasopressin (VP) release from organ-cultured explants of the hypothalamo-neurohypophyseal system (HNS). The GABA antagonists bicuculline and picrotoxin stimulated VP release in a concentration-dependent manner. These observations suggest that VP release by HNS explants is tonically inhibited by GABA. Exposure of HNS explants to GABA (10(-8)-10(-3) M) did not consistently alter basal VP release. This was true even when penicillin, which can block GABA-activated chloride channels, was omitted from the medium. Similarly, nipecotic acid, an agent that potentiates GABA activity by inhibiting GABA uptake, did not alter basal VP release; stimulation of VP release by acetylcholine and increases in osmolality was not diminished by the addition of 10(-5) M GABA. The failure of exogenous GABA to modify basal and stimulated VP release suggests that GABAergic inhibition of VP release is maximally activated by endogenously released GABA in cultured HNS explants. This is consistent with evidence for a local source of GABA in the supraoptic nucleus and suggests that one role of GABA in the regulation of VP release is that of a potent local inhibitory neurotransmitter.