ROLE OF GABAERGIC NEURONS IN AUTONOMIC NUCLEI

伽巴能神经元在自主核中的作用

• 批准号: 3476984
• 负责人: BANG H HWANG
• 金额: $ 6.94万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476984
• 关键词: GABA receptor; aminoacid inhibitor; autonomic disorder; autoradiography; benzodiazepine receptor; benzodiazepines; bicuculline; cardiovascular pharmacology; central neural pathway /tract; experimental brain lesion; gamma aminobutyrate; high performance liquid chromatography; histochemistry /cytochemistry; hypertension; hypothalamus; immunocytochemistry; in situ hybridization; innervation; laboratory rat; neuroendocrine system; neurotoxins; neurotransmitter metabolism; pituitary gonadal axis; radioimmunoassay; radiotracer; solitary tract nucleus; spontaneous hypertensive rat; vasopressins

Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Central administration of GABA and its agonists lowers blood pressure, but it is little known as to which and how GABA systems are involved in the cardiovascular regulation. The primary goal of this proposal is to elucidate the role of GABAergic neurons in regulation of the vasopressin (VP) neurons in (a) the paraventricular hypothalamic nucleus (PVN) - nucleus tractus solitarius (NTS) autonomic pathway, and (b) the PVN - pituitary neuroendocrine axis. However, my long-term objective is to study mechanisms by which central GABAergic neurons modulate blood pressure. Electron microscopic immunocytochemistry, high performance liquid chromatography, radiometric assay (for glutamate decarboxylase, GAD), radioimmunoassay (for detecting VP contents), in situ hybridization (for studying VP mRNA), and quantitative receptor autoradiography will be applied to evaluate the GABA and VP neurons of spontaneously hypertensive (SHR) rats. More specifically, this proposal is: 1) to reveal GABAergic neurons supplying the PVN, lateral "circumventricular" region (LCV), and NTS; 2) to characterize GAD activities, GABA synaptogenesis, GABA contents, GABA turnover and GABA receptors in the PVN, LCV, and NTS of SHR rats; 3) to evaluate the relationship between GABA parameters and VP parameters (i.e., VP mRNA and VP contents) in the PVN; 4) to study whether receptors for benzodiazepines (which are closely interacted with endogenous GABA), are in conjunction with GABA receptors to associate with hypertension; 5) to determine whether and how changes of GABA/VP parameters in the PVN are correlated with GABA/VP parameters in the NTS during the development of hypertension; and 6) to verify that there are functional GABA receptors in the PVN to regulate VP, by studying VP contents in the NTS, pituitary and plasma after microinjections of a GABA antagonist into the PVN. These studies may provide new information on the neural basis of hypertension associated with GABA/VP neurons, which will be useful for drug developments aimed at the treatment or prevention of hypertension.

伽马氨基丁酸（GABA）是一种主要的抑制 大脑中的神经递质。 GABA中央管理 它的激动剂降低了血压，但鲜为人知 GABA系统如何参与心血管 规定。 该提议的主要目标是阐明 GABA能神经元在调节加压素（VP）中的作用 （a）旁丘脑下丘脑核（PVN）的神经元 - 小核巨石Solitarius（NTS）自主途径，（b） PVN-垂体神经内分泌轴。 但是，我的长期 目的是研究中央GABA能的机制 神经元调节血压。 电子显微镜免疫细胞化学，高性能 液相色谱法，辐射测定法（用于谷氨酸 脱羧酶，GAD），放射免疫测定（用于检测VP 内容），原位杂交（用于研究VP mRNA）和 定量受体放射自显影将用于评估 自发性高血压（SHR）的GABA和VP神经元 老鼠。 更具体地说，该建议是：1）揭示Gabaergic 提供PVN的，外侧“环形”区域的神经元 （LCV）和NTS； 2）表征GAD活动，GABA 突触发生，GABA内容，GABA离职和GABA SHR大鼠的PVN，LCV和NTS中的受体； 3）评估 GABA参数与VP参数之间的关系 （即VP mRNA和VP内容）在PVN中； 4）研究是否 苯二氮卓类药物的受体（与之紧密相互作用 内源性GABA），与GABA受体结合 与高血压交往； 5）确定是否以及如何 PVN中GABA/VP参数的变化与 NTS中的GABA/VP参数在开发过程中 高血压; 6）验证是否有功能性GABA PVN中的受体调节VP，通过研究VP中的含量 GABA显微注射后的NTS，垂体和血浆 拮抗剂进入PVN。 这些研究可能会提供有关神经基础的新信息 与GABA/VP神经元相关的高血压，这将是 对于针对治疗的药物开发有用或 预防高血压。