NEUROHORMONAL MECHANISMS OF SALT APPETITE

这个项目的主要目标是研究细胞 肾上腺类固醇调节的分子机制 他们在控制食欲方面的行为。 肾上腺类固醇作用于大脑，唤起钠的食欲和 通过激活大脑血管紧张素系统以及通过 抑制催产素(OT)等抑制性神经肽系统 和速激肽(TKS)。这些效应是由基因组介导的。 盐皮质激素和糖皮质激素的作用机制 在整个大脑中表达的受体作用于 与非基因组机制协调一致。我们揭开了一部小说， 肾上腺类固醇在杏仁核中的非基因组作用 将我们的注意力集中在这个大脑区域，以及 GABA-苯二氮卓类受体系统。相互关联的具体内容 AIMS旨在详细说明基因组和非基因组 肾上腺类固醇的神经肽作用机制 体系和GABA-苯二氮卓体系及其相互作用 在钠的食欲的唤醒中相互作用。具体的 研究目的：1)基因控制食盐食欲 使用反义的盐皮质激素和糖皮质激素受体 技术；2)杏仁核对食盐的非基因组控制 使用局部应用类固醇和 苯二氮类激动剂和拮抗剂；3)基因组参与 控制关键神经肽的表达 对食盐的兴奋或抑制；4)相互作用 神经肽水平上的基因组和非基因组机制 和GABAA受体。需要测试的具体假设包括 一种涉及矿物皮质激素的基因组机制的观点 受体维持GABAA和神经肽的关键成分 系统处于一种可以发生非基因组行为的状态。 另一种假设是，非基因组类固醇的作用包括 直接作用于GABAA的产物的类固醇代谢 受体，以增加其功效。这项研究与 理解饮食的行为和神经控制的作用 盐的摄入量，这有助于建立和 高血压的维持。

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.