NEUROHORMONAL MECHANISMS OF SALT APPETITE

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 他们的行为对控制钠食欲的作用。 肾上腺类固醇作用于大脑，引起钠食欲， 通过激活大脑血管紧张素系统以及 抑制神经肽系统，如催产素（OT） 和速激肽（TKs）。这些作用是由基因组介导的。 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， 与非基因组机制相一致。我们发现了一本小说， 杏仁核中肾上腺类固醇的非基因组作用， 将我们的注意力集中在这个大脑区域，以及 GABA-苯二氮卓受体系统。相关具体 目的是阐述基因组和非基因组 肾上腺皮质类固醇作用的神经肽机制 系统和GABA-苯并二氮杂卓系统及其相互作用 在激发钠的食欲时相互作用。具体 研究目的：1）盐食欲的基因组控制，包括 盐皮质激素和糖皮质激素受体使用反义 2）杏仁核中盐食欲的非基因组控制 使用局部应用类固醇和 苯二氮卓激动剂和拮抗剂; 3）基因组参与 控制关键神经肽的表达， 兴奋或抑制盐食欲; 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。 有待检验的具体假设包括 盐皮质激素的基因机制 受体维持GABA a和神经肽的关键成分 系统处于非基因组行为可以发生的状态。 另一种假设是，非基因组类固醇作用涉及 类固醇代谢为直接作用于GABA a的产物 受体，以提高其功效。这项研究与 了解饮食的行为和神经控制的作用 盐的摄入，这有助于建立和 维持高血压。

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.