NEURAL REGULATION OF THIRST

口渴的神经调节

• 批准号: 2264696
• 负责人: MASSAKO KADEKARO-KUTYNA
• 金额: $ 24.31万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2264696
• 关键词: amine oxidoreductase; aminoacid analog; angiotensin II; arginine; body fluids; body water dehydration; brain metabolism; cell morphology; electrolyte balance; endogenous opioid; enzyme inhibitors; hormone regulation /control mechanism; laboratory rat; neural information processing; neuroendocrine system; nitric oxide; opioid receptor; oxytocin; receptor sensitivity; thirst; water drinking behavior

Nitric oxide (NO) is a newly discovered lipophilic gas synthesized by NO synthase (NOS) in the central nervous system that can alter short- and long-term synaptic function. There is now good evidence that NO is synthesized in neural structures essential for the regulation of salt- water balance. Specifically, this network includes magnocellular neurons in the supraoptic and paraventricular nuclei, where oxytocin (OT) and vasopressin (VP) are synthesized, and the subfornical organ (SFO), involved in drinking behavior. NO could, therefore, modulate water balance by influencing activity of neurons at these sites. Our preliminary studies demonstrated that blockade of NOS with NG-monomethyl- L arginine (NMMA) administered intracerebroventricularly (icv) enhances secretion of OT, but not VP, and attenuates water intake in 24h dehydrated rats. These results indicate that NO promotes rehydration by regulating neural mechanisms controlling drinking behavior and the preferential release of VP over OT during dehydration. We propose to examine further the role of NO in the modulation of neurosecretory function and drinking behavior in response to osmotic stimulation, hemorrhage and angiotensin II stimulation. NMMA will be injected icv to conscious rats under these conditions of reduced intracellular or extracellular volume to determine if NO influences release of OT drinking behavior. We will then investigate if the modulatory role of NO on OT release involves participation of endogenous opioid peptide (EOP) since both NMMA and blockade of opiate receptors with naloxone enhance the rise in plasma OT without changing glucose utilization in the hypothalamo- neurohypophysial system during dehydration. Two possibilities will be tested: a) If the attenuation of OT release during dehydration is mediated by NO facilitating secretion of an EOP (NO EOP OT), then icv injection of L-arginine, the substrate for NOS, should decrease or prevent the effect of norbinaltorphimine, a kappa opiate receptor antagonist. b) If this attenuation of OT secretion is mediated by an EOP faciliting formation of NO (EOP NO OT), then icv injection of dynorphin-A (1-8), a kappa receptor agonist, should decrease or prevent the effect of NMMA. Because regulation of salt-water balance is closely linked t mechanisms affecting arterial blood pressure, this study may provide important clinical information regarding preventive medicine applied to hypertension.

一氧化氮（NO）是新发现的由NO合成的亲脂性气体 中枢神经系统中的合酶（NOS）可以改变短和 长期突触功能。 现在有充分的证据表明NO是 在调节盐所必需的神经结构中合成 水平衡。 具体来说，该网络包括大细胞神经元 在视上核和室旁核中，催产素 (OT) 和 合成加压素 (VP)，穹窿下器官 (SFO) 涉及饮酒行为。 因此，NO 可以调节水 通过影响这些部位神经元的活动来实现平衡。 我们的 初步研究表明，用 NG-monomethyl- 阻断 NOS 脑室内 (icv) 给予左旋精氨酸 (NMMA) 可增强 分泌 OT，但不分泌 VP，并减少 24 小时内的饮水量 脱水的老鼠。 这些结果表明，NO 通过以下方式促进补液： 调节控制饮酒行为的神经机制 脱水期间 VP 优先于 OT 释放。 我们建议 进一步研究NO在神经分泌调节中的作用 对渗透刺激的反应的功能和饮酒行为， 出血和血管紧张素II刺激。 NMMA将被注射icv 在细胞内或细胞内减少的条件下有意识的大鼠 细胞外体积以确定 NO 是否影响 OT 饮酒的释放 行为。 然后我们将研究 NO 对 OT 的调节作用 释放涉及内源性阿片肽（EOP）的参与，因为 NMMA 和用纳洛酮阻断阿片受体都会促进升高 在血浆 OT 中不改变下丘脑的葡萄糖利用 脱水期间的神经垂体系统。 将有两种可能 测试： a) 如果脱水过程中 OT 释放的衰减是 由 NO 介导，促进 EOP 的分泌（NO EOP OT），然后是 icv NOS 底物 L-精氨酸的注射量应减少或 防止去甲吗托菲明（一种 kappa 阿片受体）的作用 对手。 b) 如果 OT 分泌的减弱是由 EOP 介导的 促进NO形成（EOP NO OT），然后静脉注射强啡肽-A (1-8)，一种κ受体激动剂，应减少或阻止该作用 NMMA 的。 因为盐水平衡的调节与水盐平衡密切相关。 影响动脉血压的机制，这项研究可能提供 有关预防医学应用的重要临床信息 高血压。