ATRIAL NATRIURETIC PEPTIDE & ALDOSTERONE SECRETION

心房钠尿肽

• 批准号: 3352416
• 负责人: PAULA Q BARRETT
• 金额: $ 19.69万
• 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 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352416
• 关键词: G protein; aldosterone; angiotensin II; animal tissue; antihypertensive agents; atrial natriuretic peptide; calcium channel; congestive heart failure; cyclic nucleoside monophosphate; electrolyte balance; electrophysiology; fluorescence spectrometry; hormone regulation /control mechanism; hypertension; phosphomonoesterases; radioimmunoassay; secretion; steroid biosynthesis

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.

心房尿液肽（ANP），一种有效的利尿剂和脂肪酸 激素，整个体内都有受体，包括中枢神经 系统，肾脏，平滑肌和肾上腺皮质。 一种理解 该肽的作用机理将提供对 确定体积和血压的主要反调节效应子 人类体内平衡。 这项研究重点是阐明 ANP在肾上腺肾小球中的作用抑制了合成 和醛固酮的分泌。 这种抑制作用本身很重要 生理意义，因为醛固酮是盐的主要调节剂 和肾脏中的水吸收，并在其分泌 在临床上与高血压和水肿有关 充血性心力衰竭和肝肝硬化等州。 职业 ANP受体（S）通过独特的鸟苷酸诱导CGMP增加 富含循环酶的受体和通过受体/G蛋白的cAMP降低 相互作用。 在肾小球细胞中，第二个目标的目标 信使仍然未知，尽管电压的差异调制 - ANP依赖CA2+渠道及其对 维持类固醇生成表明CA2+通道可能是 规定。 该项目的具体目的是确定： ANP调节Ca2+通道的机制，其他 Ca2+依赖性蛋白激酶以及CGMP与膜的关系 ANP诱导的类固醇发生的潜力。 这些研究 将涉及电压门控通道的贴片钳分析， 膜的电生理和光谱测定测定 潜力，使用激酶激活测定和蛋白质印迹 循环核苷酸和醛固酮的技术和放射免疫测定。 结果，该项目将阐明ANP的机制 改变Ca2+流入信号的产生及其接收到Ca2+ - 依赖性效应子，将有助于我们对低调的理解 高血压状态。