Osmotic activation of the hypothalamo-neurohypophysial system reversibly downregulates the NMDA receptor subunit, NR2B, in the supraoptic nucleus of the hypothalamus
Osmotic activation of the hypothalamo-neurohypophysial system reversibly downregulates the NMDA receptor subunit, NR2B, in the supraoptic nucleus of the hypothalamus
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DOI：
10.1016/s0169-328x(99)00129-1
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发表时间：
1999-07-05
期刊：
影响因子：
--
通讯作者：
Dao, J
中科院分区：
文献类型：
--
作者：
Currás-Collazo, M;Dao, J
NMDA受体激活在下丘脑视上核（SON）的大细胞神经内分泌细胞（MNCs）中产生特征性的神经元放电模式，其与体内和体外更大的激素释放相关。此外，i. c. v.给予NMDA受体阻滞剂抑制脱水诱导的血浆加压素和饮酒升高。为了研究NMDA受体亚单位在下丘脑大细胞神经内分泌细胞的神经内分泌功能中的作用，我们研究了渗透刺激对NMDA受体亚单位NR 1和NR 2B蛋白表达的影响，NR 1和NR 2B分别在结合甘氨酸和谷氨酸中起重要作用。取对照组大鼠和饮用2%盐水4-10天的大鼠的SON、下丘脑室旁核（PVN）、皮质和外侧下丘脑的匀浆进行SDS-PAGE和Western blot分析。该盐水饮用方案产生血浆渗透压浓度水平的显著升高。NR 1和NR 2B免疫反应性检测SON，PVN，外侧下丘脑和皮质，但不使用亚单位特异性多克隆抗体和定量使用计算机辅助光密度法在肝匀浆。平均NR 2B免疫反应性显着低于SON（29%）和PVN匀浆（23%）从盐水处理的大鼠比对照组大鼠。此外，脱水对NR 2B的影响具有区域特异性，因为在皮层和外侧下丘脑匀浆中未观察到NR 2B表达的显著变化。再水化允许血浆渗透压以及SON中的NR 2B蛋白水平恢复。这些结果表明，NMDA受体亚基表达的变化有助于大细胞神经内分泌细胞的可塑性表现在下丘脑-神经垂体系统的渗透激活。此外，我们的研究结果表明，在SON和PVN的MNCs上的NMDA受体可能有助于与体液平衡相关的神经内分泌功能。(C)1999 Elsevier Science B. V.保留所有权利。
NMDA receptor activation produces a characteristic pattern of neuronal firing in magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus of the hypothalamus (SON) which has been associated with greater hormone release in vivo and in vitro. In addition, i.c.v. administered NMDA receptor blockers suppress the dehydration-induced rise in plasma vasopressin and drinking. To investigate the role of NMDA receptor subunits in the neuroendocrine functions of the magnocellular neuroendocrine cells of the hypothalamus, we examined the effects of osmotic stimulation on the protein expression of the NMDA receptor subunits, NR1 and NR2B, important in binding glycine and glutamate, respectively. Homogenates of SON, paraventricular nucleus of the hypothalamus (PVN), cortex and lateral hypothalamus from control rats and rats given 2% saline water to drink for 4-10 days were subjected to SDS-PAGE and Western blot analysis. This saline water drinking regimen produced a significant rise in plasma osmolality levels. NR1 and NR2B immunoreactivity was detected in SON, PVN, lateral hypothalamus and cortex but not in Liver homogenates using subunit-specific polyclonal antibodies and quantified using computer-assisted densitometry. Mean NR2B immunoreactivity was significantly lower in SON (29%) and PVN homogenates (23%) from saline-treated rats than in those from control rats. In addition, the effect of dehydration on NR2B was regionally specific since no significant changes in NR2B expression were observed in homogenates of cortex and lateral hypothalamus. Rehydration allowed recovery of plasma osmolality as well as NR2B protein levels in the SON. These results suggest that changes in NMDA receptor subunit expression contribute to the plasticity manifested by in magnocellular neuroendocrine cells in response to osmotic activation of the hypothalamo-neurohypophysial system. In addition, our results indicate that NMDA receptors on SON and PVN MNCs may contribute to neuroendocrinological functions associated with body fluid homeostasis. (C) 1999 Elsevier Science B.V. All rights reserved.