UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 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

Vasopressin and oxytocin neuroendocrine cells within the supraoptic nucleus of the adult hypothalamus (SON) display mRNA expression for the NMDA receptor subunits, NR1 and NR2B, NR2C and NR2D. The NR2B subunit confers slow decay kinetics (relative to NR1/NR2A receptors) and high magnesium sensitivity to NMDA receptor responses--properties which may contribute to the NMDA receptor-mediated bursting manifested by these cells. Therefore, we examined NR2B protein expression and its developmental profile in the SON and compared it to that in the cortex and cerebellum--areas which have been studied previously. We performed Western blot analysis on SON homogenates from embryonic, postnatal (PN7, 14, 21), and adult rats using an NR2B-specific antibody. Adult NR2B levels in the SON and PVN were similar but low relative to those of cortex. SON NR2B protein levels rose in the first postnatal week, remained high through PN21, and later declined to significantly lower levels in the adult. A similar profile was observed in cerebellum, where NR2B expression displayed a sharp peak at PN14 and later declined to minimal or undetectable levels in the adult. In contrast, NR2B continued to be overexpressed through adulthood in the cortex. The ontogenic pattern for NR1 expression, which included unregulation during early postnatal life and adulthood, was similar in the SON and cortex. A different pattern was observed for the cerebellum, where NR1 levels increased gradually after ED17 to reach significantly greater adult levels. Of all three areas studied, the SON displayed the earliest developmental rise in NR1 levels. SON explant cultures proved to be a useful preparation, since they contained neurons which synthesized NR1 and NR2B subunits in quantities similar to those of ED17 SON. Our findings suggest that NMDA receptors on SON neuroendocrine cells are assembled using NR1 and NR2B subunits, and that their plastic expression in early postnatal life may play a role during development.
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PMID:Developmental plasticity of NR1 and NR2B subunit expression in the supraoptic nucleus of the rat hypothalamus. 970 87

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