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)

Vasopressin and oxytocin neuroendocrine cells within the supraoptic nucleus display distinctive electrophysiological properties and differential responses to selected NMDA receptor (NR) antagonists. To determine if these differences might be due to NMDA receptor composition, we compared the expression of NR1, NR2A, NR2B, NR2C and NR2D subunit mRNAs in immunocytochemically identified vasopressin and oxytocin neuroendocrine cells. In contrast to NR1 subunit mRNA which was equally expressed in both vasopressin and oxytocin cells, NR2B and NR2C displayed very different expression patterns. In oxytocin cells, the NR2B subunit comprised the majority (65%) of the total NR2 expression with NR2C and NR2D contributing 6% and 27%, respectively. Vasopressin cells exhibited 5-fold higher NR2C (32%), approximately half as much NR2B mRNA (39%) and equivalent NR2D (31%). In vitro expression studies have shown that the NR1-NR2C subunit combination exhibits weaker magnesium block and higher affinity for glycine than NR1-NR2B. Thus, the high expression of NR2C in vasopressin cells relative to oxytocin cells may make these cells more susceptible to glutamatergic activation. These observations in vasopressin and oxytocin cells provide the basis for a working model to investigate how differential NMDA receptor composition may shape the neurophysiological properties of neurons.
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PMID:Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in vasopressin and oxytocin neuroendocrine cells. 907 68

Intense electrical activity throughout the brain which results from generalized epileptic or kindled seizures is thought to cause persistent and widespread neuronal plastic changes. We have previously reported that stage 5 kindled seizures cause an increase in vasopressin messenger RNA content and nitric oxide synthase activity in neuroendocrine cells of the supraoptic nucleus which lasts for at least four months after the last seizure. To evaluate whether changes in the expression of N-methyl-D-aspartate receptor subunits might contribute to these effects, the expression of NR1, NR2A, NR2B. NR2C and NR2D subunit messenger RNAs was examined by in situ hybridization in neuroendocrine cells of the supraoptic nucleus one month after amygdala kindling to stage 5 seizures. No change in NR1 subunit messenger RNA expression was seen. In contrast, NR2B subunit messenger RNA was significantly increased. by about 63%, and NR2D subunit messenger RNA was significantly decreased, by about 22%. indicating a shift in NR2 subunit messenger RNA expression. NR2B subunit messenger RNA was also significantly increased in adjacent limbic structures. The long-lasting shift towards increased NR2B and decreased NR2D messenger RNA expression after kindling suggests that N-methyl-D-aspartate receptor NR2 composition may be an important factor in the maintenance of pathological plasticity following generalized seizures. If these changes in messenger RNA are translated into increased NR2B and decreased NR2D subunits in the N-methyl-D-aspartate receptors in vivo, both a decrease in sensitivity due to a strong magnesium block and an increase in channel ion gating might be predicted.
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PMID:Amygdala kindling alters N-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus. 913 Jul 80

The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory neurons (MNC) which synthesize and release the peptide hormones vasopressin and oxytocin. Glutamate is a prominent excitatory neurotransmitter in the SON and regulates MNC excitability. NMDA receptors (NMDAR), a type of ionotropic glutamate receptor, mediate synaptic plasticity of MNCs and are necessary for characteristic burst firing patterns which serve to maximize hormone release. NMDARs are di- or tri-heteromeric complexes of NR1 and NR2 subunits. Receptor properties depend on NR2 subunit composition and variable splicing of NR1. We investigated the expression profile of NR1 and NR2 subunits in the SON at the mRNA and protein levels plus protein expression of NR1 splice variants in control and salt-loaded adult rats. There was robust mRNA expression of all subunits, with NR2D levels being the highest. At the protein level, NR1, NR2B, and NR2D were robustly expressed, while NR2A was weakly expressed. NR2C protein was not detected with either of the two antibodies tested. All four NR1 splice variant cassettes (N1, C1, C2, C2') were detected in the SON, although NR1 N1 expression was too low for accurate analysis. Three days of salt-loading did not alter mRNA, protein, or splice variant expression of NMDAR subunits in the SON. Robust NR2D protein expression has not been previously shown in MNCs and is uncommon in the adult brain. Although the functional significance of this unusual expression profile is unknown, it may contribute to important physiological characteristics of SON neurons, such as burst firing and resistance to excitotoxicity.
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PMID:NMDA receptor subunit expression in the supraoptic nucleus of adult rats: dominance of NR2B and NR2D. 2139 92

In addition to producing a classical excitatory postsynaptic current via activation of synaptic NMDA receptors (NMDARs), glutamate in the brain also induces a tonic NMDAR receptor current (I_NMDA) via activation of extrasynaptic NMDARs (eNMDARs). However, since Mg²⁺ blocks NMDARs in non-depolarized neurons, the potential contribution of eNMDARs to the overall neuronal excitation/inhibition balance remains unknown. Here, we demonstrate that chronic (7-day) salt loading (SL) recruited NR2D subunit-containing NMDARs to generate an Mg²⁺-resistant tonic I_NMDA in non-depolarized (V_h, -70 mV) vasopressin (VP) (but not oxytocin (OT)) supraoptic nucleus (SON) neurons in male rodents. Conversely, in euhydrated and 3-day SL mice, Mg²⁺-resistant tonic I_NMDA was not observed. Pharmacological and genetic intervention of NR2D subunits blocked the Mg²⁺-resistant tonic I_NMDA in VP neurons under SL conditions, while an NR2B antagonist unveiled Mg²⁺-sensitive tonic I_NMDA but not Mg²⁺-resistant tonic I_NMDA In the EU-group VP neurons, an Mg²⁺-resistant tonic I_NMDA was not generated by increased ambient glutamate or treatment with co-agonists (e.g., d-serine and glycine). Chronic SL significantly increased NR2D expression but not NR2B expression in the SON relative to the EU group or after 3 days under SL conditions. Finally, Mg²⁺-resistant tonic I_NMDA selectively upregulated neuronal excitability in VP neurons under SL conditions, independent of ionotropic GABAergic input. Our results indicate that activation of NR2D-containing NMDARs constitutes a novel mechanism that generates an Mg²⁺-resistant tonic I_NMDA in non-depolarized VP neurons, thus causing an excitatory E/I balance shift in VP neurons to compensate for the hormonal demands imposed by a chronic osmotic challenge.SIGNIFICANCE STATEMENT:The hypothalamic supraoptic nucleus (SON) consists of two different types of magnocellular neurosecretory cells (MNCs) that synthesize and release two peptide hormones: vasopressin (VP), necessary for regulation of fluid homeostasis, and oxytocin (OT), which plays a major role in lactation and parturition. NMDA receptors (NMDARs) play important roles in shaping neuronal firing patterns and hormone release from the SON MNCs in response to various physiological challenges. Our results show that prolonged (7-day) salt loading generated a Mg²⁺ resistant tonic NMDA current mediated by NR2D subunit-containing receptors, which efficiently activated non-depolarized VP (but not OT) neurons. Our findings support the hypothesis that NR2D subunit-containing NMDARs play an important adaptive role in adult brain in response to a sustained osmotic challenge.
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PMID:High salt intake recruits tonic activation of NR2D subunit-containing extrasynaptic NMDARs in vasopressin neurons. 3330 77