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)

Supraoptic neurosecretory neurons express a prominent N-methyl-D-aspartate receptor system. Recent in vitro evidence reveals that N-methyl-D-aspartate receptor activation dramatically alters the spontaneous discharge patterns of supraoptic neurons. In this study we evaluate whether N-methyl-D-aspartate receptors in vivo contribute to the development of characteristic phasic discharge patterns displayed by vasopressin-secreting neurons. Intravenous administration of ketamine hydrochloride, a non-competitive N-methyl-D-aspartate receptor antagonist, was used to examine whether N-methyl-D-aspartate receptor blockade influences patterned spontaneous discharge observed in supraoptic neurosecretory neurons. Extracellular recordings were obtained from identified hypothalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats. Systemic administration of ketamine (< or = 1.5 mg/kg) potently suppressed spontaneous phasic discharge in 16/19 putative vasopressin-secreting cells. The ketamine-induced blockade was dose dependent, fully reversible and was associated with the complete blockade of activity evoked by local pressure application of N-methyl-D-aspartate, but not the activity evoked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no detectable effect on threshold or shape of antidromic action potentials. By comparison, the activity in 9/10 continuously active neurons (putative oxytocin-secreting) was unaffected by administration of identical doses of ketamine. These data suggest that N-methyl-D-aspartate receptors play an important role in regulating the onset and maintenance of spontaneous phasic activity patterns displayed by rat supraoptic vasopressin neurons in vivo.
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PMID:N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo. 751 67

1. Vasopressin-secreting neurones in the rat hypothalamic supraoptic nucleus display patterned spontaneous phasic activity, which is apparently maintained in vivo through yet unidentified neurotransmitter system(s). The present investigation used extracellular recording techniques in anaesthetized Long-Evans rats to evaluate whether the neurotransmitter mechanism underlying phasic firing is provided via a family of ionotropic glutamate receptors. 2. N-Methyl-D-aspartate (NMDA) reliably evoked bursts of activity in twenty-seven of twenty-eight phasic neurones. Amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainate also elicited pronounced excitations in twenty-one of twenty-one and and fourteen of fifteen phasic cells, respectively. 3. A rapid blockade of on-going phasic activity was consistently induced following brief applications of both NMDA and non-NMDA receptor antagonists; extended application of antagonists resulted in prolonged silent periods, during which phasic activity failed to recur for minutes. Neither saline nor a cholecystokinin receptor antagonist influenced cell firing. 4. In contrast to putative vasopressin cells, application of NMDA receptor ligands did not affect the spontaneous activity in most putative oxytocin-secreting neurones, whereas kainate and AMPA potently excited seven of nine and four of five putative oxytocin cells, respectively. 5. These results imply that the maintenance of spontaneous phasic discharges in vivo in supraoptic vasopressin-secreting neurones requires tonic synaptic activation involving both NMDA and non-NMDA glutamate receptors. In putative oxytocin-secreting neurones, spontaneous firing appears to be predominantly regulated by non-NMDA receptors. Glutamatergic innervations may be in a unique position to influence the genesis of patterned electrical activity in supraoptic vasopressin neurones.
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PMID:Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurones in vivo by glutamate receptors. 754 68

The cellular localization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor, GluR3, was identified using antibodies that recognize the N-terminus of the predicted polypeptide sequence of GluR3. Regional immunoblot analysis of monkey brain homogenates identified a protein of approximately 102,000 mol. wt that was enriched in hypothalamus. Immunocytochemistry demonstrated that GluR3 was enriched within the hypothalamic magnocellular neurosecretory nuclei and axons of the hypothalamo-neurohypophysial tract in rat and monkey. GluR3 immunoreactivity co-localized to oxytocin-containing, but not vasopressin-containing, neurons of the hypothalamic paraventricular nucleus, supraoptic nucleus and accessory magnocellular nuclei. Ultrastructurally, GluR3 immunoreactivity was enriched throughout cytoplasm of the somatodendritic compartment and was associated with postsynaptic and presynaptic structures. GluR3 immunoreactivity was frequently observed to be clustered at the plasma membrane of the somatodendritic compartment, consistent with the predicted localization of a membrane-bound ion channel. Additionally, GluR3-immunoreactive axon terminals in synaptic contact with unlabeled dendrites within the retrochiasmatic area and bed nucleus of the stria terminalis were observed, providing morphological evidence for a presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor. By immunoblot analysis and immunocytochemistry using antibodies directed against a specific alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor in rat and monkey brain, our findings suggest a highly selective hypothalamic distribution of the GluR3 subunit that may have functional significance in the glutamatergic regulation of oxytocinergic neurons.
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PMID:The AMPA glutamate receptor GluR3 is enriched in oxytocinergic magnocellular neurons and is localized at synapses. 777 69

1. It has been claimed that glutamate is the dominant excitatory neurotransmitter in neuroendocrine regulation. The evidence is derived mainly from in vitro experiments. 2. We have investigated in vivo a possible role of excitatory amino acids (EAAs) in the neural control of release of vasopressin (AVP) and oxytocin from the neurohypophysis. 3. In rats under ethanol anaesthesia in which a diuresis was maintained by a constant fluid load, the i.c.v. injection of glutamate and the synthetic agonists alpha-amino, 3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) produced an antidiuretic response (ADR) which was abolished by an AVP antagonist. For AMPA and NMDA it was shown that this ADR was accompanied by increased urinary excretion of AVP and oxytocin. 4. The selectivity of antagonists was tested in this system. D-2-Amino-5-phosphonopentanoate (D-AP5) blocked the responses to NMDA but not to AMPA; 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked the responses to both agonists. 5. The ADR to muscarine and hypertonic saline i.c.v., and the increase in excretion of AVP and oxytocin in response to muscarine, were blocked by CNQX but not by D-AP5. 6. The results suggest that hypertonic saline releases AVP and muscarine releases both AVP and oxytocin, at least in part, by activating a glutaminergic input to the SON and PVN involving an AMPA receptor. This input could function as a terminal interneurone in afferent neural pathways to these nuclei.
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PMID:Release of vasopressin and oxytocin by excitatory amino acid agonists and the effect of antagonists on release by muscarine and hypertonic saline, in the rat in vivo. 878 84

Stimulation of ascending catecholaminergic neurones of the A1 region in ventrolateral medulla by excitatory amino acids mediate neurohypophysial vasopressin secretion triggered by hypovolemic hypotension. Recent cloning of the ionotrophic excitatory amino acid receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type and subsequent production of receptor recognizing antisera have made immunocytochemical detection of receptor proteins in phenotypically characterized neurones possible. Using single immunocytochemical detection of glutamate GluR1, GluR2,3, GluR4 receptor proteins we have investigated the distribution of GluR-receptor proteins in the caudal ventrolateral medulla. In the neurones of the A1 cell group, only GluR2,3-immunoreactivity was expressed whereas GluR1-immunoreactive neurones were seen in the adjacent reticular formation. Using dual immunocytochemistry in combination with retrograde Fluorogold tracing we determined the extent of co-expression of tyrosine-hydroxylase and glutamate GluR2,3 receptor protein immunoreactivity in neurones of the A1 cell group in the ventrolateral medulla that project to the area of the paraventricular nucleus of the hypothalamus. It was seen that the majority of catecholaminergic A1 neurones of the caudal VLM that project directly to the paraventricular nucleus are also immunoreactive to the Glu R2,3 receptor protein further substantiating that these neurones are directly influenced by the excitatory amino acid glutamate.
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PMID:Neurones projecting to the hypothalamus from the brainstem A1 catecholaminergic cell group express glutamate-R2,3 receptor immunoreactivity. 882 51

Previous studies demonstrated that the increase in vasopressin (VP) release and induction of VPmRNA content by osmotic stimulation was blocked by kynurenic acid, a non-specific antagonist of excitatory amino acid (EAA) receptors. In order to identify the type of EAA receptor involved, perifused explants of the hypothalamo-neurohypophyseal system (HNS) were exposed to a ramp increase in osmolality (40 mOsm over 6 h achieved by increasing NaCl) in the presence and absence of 10 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of non-n-methyl-d-aspartate (NMDA) excitatory amino acid receptors. Vasopressin release and VP mRNA content were significantly increased by exposure to the osmotic stimulus. 6,7-dinitroquinoxaline-2,3-dione inhibited osmotically stimulated VP release (F=16.65, P=0.0008) without significantly reducing basal release. It also prevented the osmotically stimulated increase in VP mRNA content (P <0.05). Although these results implicated glutamate, the primary endogenous ligand for EAA receptors, in the regulation of VP, exogenous glutamate was ineffective in stimulating VP release from HNS explants in either low-Mg2+ or Mg2+-replete medium. However, blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor desensitization with cyclothiazide (100 microM) caused a marked increase in VP release in response to 100 microM glutamate, and blockade of kainate receptor desensitization with concanavalin A resulted in a small, but significant increase in VP release in response to 1 mM glutamate. These results support a role for non-NMDA receptor activation in osmotic regulation of VP release.
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PMID:Role of non-NMDA receptors in osmotic and glutamate stimulation of vasopressin release: effect of rapid receptor desensitization. 987 Jul 46