ATRIAL NATRIURETIC PEPTIDE AND ALDOSTERONE SECRETION

心房钠尿肽和醛固酮分泌

• 批准号: 2218329
• 负责人: PAULA Q BARRETT
• 金额: $ 21.33万
• 依托单位: UNIVERSITY OF VIRGINIA
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2218329
• 关键词: ATRIAL; NATRIURETIC; PEPTIDE; ALDOSTERONE; SECRETION

Atrial natriuretic peptide (ANP), a potent diuretic and natriuretic hormone, has receptors throughout the body, including the central nervous system, the kidney, smooth muscle and the adrenal cortex. An understanding of the mechanism of action of this peptide will provide insight into the major counter-regulatory effectors determining volume and blood pressure homeostasis in humans. This study focuses on elucidating the mechanism of action of ANP in the adrenal glomerulosa where it inhibits the synthesis and secretion of aldosterone. This inhibitory action itself has important physiological implications since aldosterone is the major regulator of salt and water reabsorption in the kidney, and derangements in its secretion have been associated clinically with high blood pressure and edematous states such as congestive heart failure and liver cirrhosis. Occupation of the ANP receptor(s) induces an increase in cGMP via a unique guanylate cyclase-containing receptor and a decrease in cAMP via a receptor/G-protein interaction. In the glomerulosa cell the targets of these second messengers remain unknown, although the differential modulation of voltage- dependent Ca2+ channels by ANP and their critical importance to the maintenance of steroidogenesis indicate that Ca2+ channels may be sites of regulation. The specific aims of this project are to determine: the mechanism by which ANP modulates Ca2+ channels, the association of other Ca2+-dependent protein kinases, and the relationship of cGMP and membrane potential to the ANP-induced inhibition of steroidogenesis. These studies will involve patch-clamp analysis of voltage-gated channels, electrophysiological and spectrofluorometric determinations of membrane potential, the use of kinase activation assays and Western blotting techniques, and radioimmunoassays for cyclic nucleotides and aldosterone. As a result this project will elucidate the mechanism(s) by which ANP alters the generation of the Ca2+ influx signal and its reception by Ca2+- dependent effectors and will contribute to our understanding of hypo- nad hypervolemic states.

心钠素(ANP)，一种有效的利尿剂和利尿剂 荷尔蒙，在全身都有受体，包括中枢神经 系统、肾脏、平滑肌和肾上腺皮质。一种理解 对这种多肽的作用机制的研究将为深入了解 决定容量和血压的主要逆调节效应器 人类体内的动态平衡。本研究旨在阐明其发病机制。 心钠素在肾上腺小球内抑制合成的作用 和醛固酮的分泌。这种抑制作用本身就具有重要的 由于醛固酮是盐的主要调节因子，因此具有生理意义 肾脏对水的重吸收，以及肾脏分泌的紊乱 在临床上与高血压和水肿症有关 充血性心力衰竭和肝硬变等状态。占用 心钠素受体(S)通过一种独特的鸟苷引起cGMP的增加 环化酶受体与cAMP通过受体/G蛋白的减少 互动。在肾小球细胞中，这些秒的靶点 信使仍然未知，尽管电压的差动调制- 心钠素依赖的钙通道及其对心脏功能的重要作用 类固醇合成的维持表明钙通道可能是 监管。该项目的具体目标是确定： 心钠素调节钙离子通道的机制，以及其他 钙依赖蛋白激酶及cGMP与膜的关系 对心钠素诱导的类固醇合成的抑制作用。这些研究 将涉及电压门控通道的膜片钳分析， 膜的电生理和荧光光谱测定 潜力，使用激酶激活试验和Western blotting 技术，以及环核苷酸和醛固酮的放射免疫分析。 因此，本项目将阐明心绞痛的发病机制(S) 改变钙离子内流信号的产生和钙离子的接收 依赖的效应器，将有助于我们对低NAD的理解 高血容量状态。