REGULATION OF ION TRANSPORT BY ATRIAL NATRIURETIC FACTOR

心房钠尿因子对离子转运的调节

• 批准号: 3240000
• 负责人: SCOTT M. O'GRADY
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3240000
• 关键词: atrial natriuretic peptide; bumetanide; fish; furosemide; hormone regulation /control mechanism; ion transport; renal tubular transport; renal tubule; sodium potassium exchanging ATPase

Electroneutral ion transport processes such as Na-K-Cl cotransport are important in vectorial salt and water movement across many epithelial tissues involved in fluid and electrolyte regulation in vertebrate animals. Na-K-Cl cotransport is known to play an important role in tubular reabsorption in the thick ascending limb of Henle's loop in the kidney. In many cases, diseases related to hypertension are controlled, in part, by inhibition of this transport system with "loop" diuretics such as furosemide or bumetanide. Recently it was established that mammalian atrial cardiocytes produce a natriuretic and diuretic substance called atrial natriuretic factor (ANF) which causes a prompt and massive natriuresis and diuresis of short duration. Its effects on GFR and its hemodynamic actions have been described in a number of laboratories, but its effects on electrolyte transport have been controversial and, until very recently, poorly documented. Recent studies with ANF on ion transport in the isolated intestinal epithelium of the winter flounder have shown that ANF is a potent inhibitor of epithelial ion transport in this tissue. The intestine of the flounder possesses a well characterized Na-K-Cl cotransport system which is inhibitable with loop diuretics and by increases in intracellular cGMP. It is a simple, relatively homogeneous epithelium similar in its transport properties to the thick ascending limb of Henle's loop in mammalian kidney. The major goals of this proposal are to establish the mechanism of inhibition of ion transport by ANF and to determine whether an ANF-like peptide serves as an endogenous regulator of intestinal ion transport in the winter flounder. This will require: 1) identification of the specific second messengers which mediate the intracellular events responsible for inhibition of ion transport, 2) characterization of ANF receptors in the intestine and their relationship to the production of second messengers and 3) identification and characterization of ANF-like peptides produced by the flounder followed by a comparison of their physical properties and natriuretic and diuretic activities with mammalian forms of ANF. Results from these studies should be useful in understanding some of the cellular mechanisms underlying effects of these peptides in diverse tissues and also provide some insight into how ion transport is regulated and modified by diuretics in mammalian kidney and, more specifically, in the thick ascending limb of Henle's loop.

电中性离子传输过程，例如 Na-K-Cl 共传输 对跨许多上皮细胞的盐和水矢量运动很重要 脊椎动物中参与液体和电解质调节的组织 动物。 Na-K-Cl 共转运已知在肾小管中发挥重要作用 肾脏亨利氏袢粗升肢的重吸收。 在 在许多情况下，与高血压相关的疾病在一定程度上可以通过以下方法得到控制： 使用“袢”利尿剂抑制该运输系统，例如 呋塞米或布美他尼。 最近确定哺乳动物 心房心肌细胞产生一种促钠尿和利尿的物质，称为 心房钠尿因子 (ANF) 会导致迅速而大量的 尿钠排泄和短时间利尿。 对 GFR 的影响及其 许多实验室已经描述了血流动力学作用，但是 它对电解质运输的影响一直存在争议，直到 最近，记录很少。 ANF 关于离子传输的最新研究 在冬鲽鱼分离的肠上皮中显示 ANF 是该组织中上皮离子转运的有效抑制剂。 比目鱼的肠道具有特征明确的 Na-K-Cl 协同转运系统可被袢利尿剂抑制 细胞内 cGMP 增加。 这是一个简单的、相对同质的 上皮的运输特性与粗升肢相似 哺乳动物肾脏中的亨利氏环。 该提案的主要目标是建立机制 ANF 抑制离子转运并确定是否存在 ANF 样 肽作为肠道离子转运的内源性调节剂 冬季比目鱼。 这需要： 1) 确定具体的 介导细胞内事件的第二信使 离子转运的抑制，2) ANF 受体的表征 肠道及其与第二信使产生的关系 3) 产生的ANF样肽的鉴定和表征 比目鱼，然后比较它们的物理特性和 哺乳动物形式的 ANF 具有利尿钠和利尿活性。 结果 这些研究应该有助于理解一些细胞 这些肽在不同组织中的潜在作用机制以及 提供一些关于离子传输如何调节和改变的见解 哺乳动物肾脏中的利尿剂，更具体地说，是在浓稠的肾脏中的利尿剂 亨利氏环的升肢。