ATRIAL NATRIURETIC PEPTIDE AND ALDOSTERONE SECRETION

心房利钠肽（ANP），一种有效的利尿剂和利钠剂 激素，在全身都有受体，包括中枢神经系统 系统、肾脏、平滑肌和肾上腺皮质。 的理解 这种肽的作用机制将提供深入了解 决定容量和血压的主要反调节效应物 人体内的稳态 本研究的重点是阐明 ANP在肾上腺小球中的作用，在那里它抑制合成 和醛固酮的分泌。 这种抑制作用本身具有重要的 由于醛固酮是盐的主要调节剂， 肾脏的水重吸收和分泌紊乱 在临床上与高血压和水肿有关 如充血性心力衰竭和肝硬化。 占领 ANP受体通过独特的鸟苷酸诱导cGMP增加 含环化酶受体和cAMP通过受体/G蛋白减少 互动 在肾小球细胞中，这些第二个靶点 信使仍然未知，虽然电压的差分调制- ANP依赖的Ca2+通道及其对 类固醇生成的维持表明，Ca 2+通道可能是 调控 该项目的具体目标是确定： ANP调节Ca2+通道的机制， Ca2+依赖性蛋白激酶，cGMP与膜的关系 潜在的ANP诱导的类固醇生成抑制。 这些研究 将涉及电压门控通道的膜片钳分析， 膜的电生理学和荧光分光光度测定 潜在的，使用激酶激活试验和蛋白质印迹法 技术和放射免疫测定环核苷酸和醛固酮。 因此，本项目将阐明ANP 改变Ca2+内流信号的产生及其被Ca2 +- 依赖性效应器，将有助于我们对Hypo-nad的理解 高血容量状态

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.