REGULATION OF ION TRANSPORT BY ATRIAL NATRIURETIC FACTOR

电子中和离子传输过程，如钠-钾-氯共传输 在许多上皮细胞的媒介盐分和水的移动中很重要 脊椎动物中与液体和电解质调节有关的组织 动物。已知Na-K-Cl共转运在肾小管中起重要作用 肾内汉勒氏环的粗大上行支重吸收。在……里面 在许多情况下，与高血压有关的疾病在一定程度上由 用“环状”利尿剂抑制这一转运系统 速尿或布美他尼。最近发现，哺乳动物 心房肌细胞产生一种利钠和利尿物质，称为 心钠素(ANF)引起的即刻和大量的 短期利钠、利尿。它对肾小球滤过率的影响及其机制 一些实验室已经描述了血液动力学行为，但 它对电解液运输的影响一直存在争议，直到 就在最近，记录很差。ANF在离子输运方面的最新研究 在冬季比目鱼的离体肠上皮细胞中 ANF是该组织中上皮离子转运的有效抑制物。 比目鱼的肠道具有很好的钠-钾-氯特性 共转运系统，可用环状利尿剂和 细胞内cGMP增加。它是一个简单的，相对同质的 上皮的运输特性与粗大的上肢相似 哺乳动物肾脏中的亨勒氏环。 这项建议的主要目标是建立 ANF对离子转运的抑制以及确定类ANF是否 多肽作为肠道离子转运的内源性调节因子 冬天的比目鱼。这将需要：1)识别特定的 调节细胞内事件的第二信使 抑制离子转运，2)心钠素受体的特性 肠道及其与第二信使和 3)产心钠素样多肽的鉴定和性质 比目鱼，然后比较它们的物理特性和 哺乳动物形式的ANF的利钠和利尿活性。结果 这些研究应该有助于理解一些细胞 这些多肽在不同组织中的潜在作用机制 深入了解离子传输是如何通过以下方式进行调节和修改的 哺乳动物肾脏中的利尿剂，更具体地说，在肥厚的 亨勒氏环的上肢。

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.