NEUROHORMONAL MECHANISMS OF SALT APPETITE

盐食欲的神经激素机制

• 批准号: 6111420
• 负责人: Bruce S. McEwen
• 金额: $ 21.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6111420
• 关键词: GABA receptor; aldosterone; amygdala; angiotensinogen; antisense nucleic acid; benzodiazepine receptor; brain mapping; corticosteroid receptors; desoxycorticosterone; hormone regulation /control mechanism; laboratory rat; neuroendocrine system; neurohormones; neuroregulation; nutrition related tag; oxytocin; renin angiotensin system; salt intake; steroid hormone metabolism; tachykinin

The primary goal of this project is to investigate the cellular and molecular mechanisms through which adrenal steroids mediate their behavioral actions on the control of sodium appetite. Adrenal steroids act upon the brain to arouse sodium appetite and do so by activating the brain angiotensin system as well as by suppressing inhibitory neuropeptide systems such as oxytocin (OT) and the tachykinins (TKs). These effects are mediated by genomic mechanisms involving mineralocorticoid and glucocorticoid receptors that are expressed throughout the brain acting in concert with non-genomic mechanisms. We have uncovered a novel, nongenomic action of adrenal steroids in the amygdala that has focussed our attention on this brain region, as well as upon the GABA-benzodiazepine receptor system. The interrelated Specific Aims are intended to elaborate on the genomic and non-genomic mechanisms of adrenal steroid action in terms of the neuropeptide systems and the GABA-benzodiazepine system and their interactions with each other in the arousal of sodium appetite. The Specific Aims investigate: 1) Genomic control of salt appetite involving mineralocorticoid and glucocorticoid receptors using the antisense technique; 2) Non-genomic control of salt appetite in the amygdala of the rat brain using local application of steroids and benzodiazepine agonists and antagonists; 3) Involvement of genomic control of the expression of key neuropeptides that are either excitatory or inhibitory for salt appetite; 4) Interaction of genomic and non-genomic mechanisms at the level of neuropeptides and GABAa receptors. Specific hypotheses to be tested include the notion that a genomic mechanism involving mineralocorticoid receptors maintains key components of the GABAa and neuropeptide systems in a state where the non-genomic actions can take place. Another hypothesis is that the non-genomic steroid action involves steroid metabolism to products that act directly upon the GABAa receptor to increase its efficacy. This research is relevant to understanding the role of behavioral and neural control of dietary salt intake, which contributes to the establishment and maintenance of hypertension.

该项目的主要目标是研究细胞 以及肾上腺类固醇介导的分子机制 他们对钠食欲控制的行为行为。 肾上腺类固醇对大脑作用，以唤起钠食欲和 通过激活脑血管紧张素系统以及通过 抑制抑制性神经肽系统，例如催产素（OT） 和旋转金蛋白（TKS）。这些作用是由基因组介导的 涉及盐皮质激素和糖皮质激素的机制 在整个大脑中表达的受体作用 与非基因组机制的音乐会。我们发现了一本小说， 杏仁核中肾上腺类固醇的非原位作用 将我们的注意力集中在这个大脑区域以及 GABA-苯二氮卓受体系统。相互关联的特定 目的旨在详细说明基因组和非基因组。 肾上腺类固醇作用的机制在神经肽方面 系统和Gaba-Benzodiazepine系统及其相互作用 在钠食性的唤醒中彼此之间。具体 目的调查：1）涉及盐食欲的基因组控制 矿物皮质激素和糖皮质激素受体使用反义 技术; 2）杏仁核中盐食欲的非基因组控制 使用类固醇的局部应用大鼠脑的大脑和 苯二氮卓激动剂和拮抗剂； 3）基因组的参与 控制关键神经肽的表达 食欲的兴奋性或抑制作用； 4）相互作用 神经肽水平的基因组和非基因组机制 和GABAA受体。 要测试的具体假设包括 概念是一种涉及盐皮质激素的基因组机制 受体保持GABAA和神经肽的关键组成部分 处于非基因组动作的状态。 另一个假设是非基因组类固醇作用涉及 直接作用于GABAA的产品的类固醇代谢 受体提高其功效。这项研究与 了解饮食的行为和神经控制的作用 盐摄入，有助于建立和 维持高血压。