CELLULAR AND MOLECULAR ANALYSIS OF NEUROPEPTIDE REGULATION OF SALT APPETITE

神经肽调节盐食欲的细胞和分子分析

• 批准号: 6243041
• 负责人: STEVEN J FLUHARTY
• 金额: $ 20.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243041
• 关键词: G protein; albino rat; aldosterone; angiotensin II; antisense nucleic acid; astrocytes; autoradiography; brain mapping; corticosteroids; estrogens; gender difference; immunocytochemistry; neuroendocrine system; neuropeptide receptor; nuclear runoff assay; nutrition related tag; ovariectomy; oxytocin; receptor expression; salt intake; tissue /cell culture; western blottings

The primary objective of this project is to investigate the cellular and molecular properties of neuronal receptors for two neuropeptides, angiotensin II (AngII) and oxytocin (OT). It is now well established that each of these peptides play prominent and opposing roles in the central regulation of sodium appetite; AngII as a major stimulatory peptide, and OT as a mediator of inhibition. The proposed experiments are divided into three main sections. In the first section, we will continue our investigations of the regulation of these neuropeptide receptors in brain by adrenal steroid hormones. In the second series of experiments, we will further investigate the cellular actions of AngII and OT, and determine how these effects are modulated by adrenal steroids. These experiments will include the use of antisense oligonucleotides to specifically and reversibly interfere with the expression of proteins (i. e. receptors, G- proteins and enzymes) involved in AngII and OT action in brain to directly examine their involvement in sodium appetite. In the final set of experiments, we will explore some of the possible mechanisms for the sexual dimorphism of sodium appetite, ascertaining the relative contributions of excitatory and inhibitory neuropeptides during estrogen modulation of salt ingestion. Collectively, these experiments should provide a fuller understanding of the cellular mechanisms that mediate neuropeptide control of salt appetite.

该项目的主要目的是调查 两种神经元受体的细胞和分子特性 神经肽，血管紧张素II（Angii）和催产素（OT）。现在 很好地确定，这些肽中的每一个都显着，并且 在钠食欲的中央调节中相反的作用； angii 作为主要的刺激性肽，OT是 抑制。提出的实验分为三个主要 部分。在第一部分，我们将继续我们的 调节这些神经肽受体的调节 在大脑中，肾上腺类固醇激素。在第二系列 实验，我们将进一步研究 Angii和OT，并确定如何调节这些效果 肾上腺类固醇。这些实验将包括使用 反义寡核苷酸特定和可逆 干扰蛋白质的表达（即受体，g- 蛋白质和酶）参与ANGII和大脑中的OT作用 直接检查他们参与钠食性。 在 最后一组实验，我们将探索一些可能的 钠食欲的性二态性的机制， 确定兴奋性和 盐调节期间抑制性神经肽 摄取。总的来说，这些实验应提供更饱满的 了解介导神经肽的细胞机制 盐食欲的控制。