CENTRAL NEURAL REGULATION OF VASOPRESSIN SECRETION

加压素分泌的中枢神经调节

• 批准号: 3395165
• 负责人: JAMES N HAYWARD
• 金额: $ 17.1万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-07-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395165
• 关键词: angiotensin II; dopamine; electron microscopy; electrophysiology; enkephalins; fresh water environment; gamma aminobutyrate; histochemistry /cytochemistry; hormone regulation /control mechanism; hypothalamus; immunochemistry; laboratory rat; neural information processing; neuroendocrine system; neurotransmitters; nicotinic receptors; norepinephrine; organ culture; parasympathetic nervous system; supraoptic nucleus; synapses; vasopressins

Our studies will focus on the chemical and physiological factors which control the secretion of vasopressin by magnocellular neurons in the hypothalamic supraoptic nucleus. These factors will be identified, characterized and an attempt will be made to relate these to the osmotic regulation of vasopressin secretion. The use of an in vitro approach with the hypothalamo-neurohypophysial complex (HNC) will give the degree of control necessary to achieve these goals. The HNC contains the entire supraoptic-neuroendocrine final common pathway including the two intact supraoptic nuclei (NSO), the supraoptico-neurohypophysial tract (SOHT) and the neurosecretory terminals of the neural lobe (NL). Every major site suspected of being involved in the osmotic regulation of vasopressin secretion is present in the HNC. The HNC explant retains osmosensitivity in vitro and can approach in vivo responsiveness. Thus, the entire functional pathway is present for the exploration of the functional integration of osmotic stimuli and the transduction of this information at the level of the supraoptic nucleus. We will characterize the release of vasopressin and establish the conditions which allow precise temporal and semi-quantitative analys of responsiveness via the SOHT. Effects of chemical and osmotic stimuli and their interactions will be characterized and will include screening for the effects of various putative neurotransmitters on the release of vasopressin (cholinergic, angiotensin II, norepinephrine, enkephalin, dopamine). In particular, we will focus on the specific contribution of the NSO with particular emphasis on the nicotinic cholinergic system which has been strongly implicated in the control of vasopressin secretion. The localization of putative nicotinic receptors on vasopressin-containing magnocellular neurons in NSO will be examined. Parallel experiments will be run to assess specific properties of these receptors which may contribute to osmotic sensitivity of the NSO. Investigation of the electrophysiological properties of identified cells in the NSO during chemical and osmotic challenges will provide detailed temporal comparison of the physiological responses with the release of vasopressin. Concomitant double- and triple-labeling procedures on dye-marked neurons will be used for cytoarchitectonic reconstruction and electron microscopic analysis of synaptic inputs on immunocytochemically-identified neurons in the NSO. Thus, the HNC explant represents a simple, viable, highly controlled mammalian neural system in which unknown physiological processes express their effects on a well defined final pathway. Ideal neuroendocrine control system.

我们的研究将集中在化学和生理因素上， 控制脑内大细胞神经元加压素的分泌 下丘脑视上核。这些因素将被识别出来， 并试图将这些与渗透性联系起来 对加压素分泌的调节。体外试验方法的应用 下丘脑-神经垂体复合体(HNC)将给出程度 实现这些目标所需的控制。HNC包含整个 视上-神经内分泌最终共同通路，包括两条完整的 视上核(NSO)、视上神经垂体束(SOHT)和 神经叶(NL)的神经分泌终末。每个主要站点 涉嫌参与加压素的渗透调节 HNC中存在分泌物。HNC外植体保持渗透敏感性 在体外，可以接近体内的响应性。因此，整个 功能通路的存在是为了探索功能 渗透刺激的整合和这一信息的传递 视上核的水平。我们将对发布的 加压素，并建立条件，使精确的时间和 通过SOHT对反应性进行半定量分析。的效果 将描述化学和渗透刺激及其相互作用 并将包括筛选各种假定的影响 神经递质对血管加压素(胆碱能、血管紧张素)释放的影响 去甲肾上腺素、脑啡肽、多巴胺)。尤其是，我们将重点关注 NSO的具体贡献，特别强调 尼古丁胆碱能系统被强烈地牵连在 控制加压素的分泌。推定烟碱的定位 NSO内含加压素的大细胞神经元上的受体将是 检查过了。将进行平行实验以评估特定的特性 这些受体可能与NSO的渗透敏感性有关。 经鉴定的细胞的电生理特性研究 NSO在化学和渗透挑战期间将提供详细的 生理反应与药物释放的时间比较 加压素。伴随而来的双重和三重标记程序 染色的神经元将用于细胞构筑重建和 三叉神经节突触传入的电子显微镜分析 免疫细胞化学鉴定NSO内的神经元。因此，HNC外植体 代表了一种简单、可行、高度受控的哺乳动物神经系统 哪些未知的生理过程表达了它们对井的影响 已确定的最终路径。理想的神经内分泌控制系统。