REGULATION OF ION TRANSPORT BY ATRIAL NATRIURETIC FACTOR

电子中性离子迁移过程，如Na-K-Cl共迁移， 在许多上皮细胞中的向量盐和水运动中重要 脊椎动物体液和电解质调节相关组织 动物 已知Na-K-Cl共转运在肾小管上皮细胞中起重要作用。 肾内亨利氏袢粗大的上行支的重吸收。 在 在许多情况下，与高血压有关的疾病部分地通过以下方式得到控制： 用“袢”利尿剂抑制该转运系统， 呋塞米或布美他尼。 最近研究表明， 心房心肌细胞产生一种利尿钠和利尿物质， 心房利钠因子（ANF），它引起迅速和大量的 尿钠排泄和短时间利尿。 它对GFR的影响及其 许多实验室已经描述了血液动力学作用，但 其对电解质转运的影响一直存在争议， 最近，记录不多。 ANF在离子转运中的最新研究 在离体的肠上皮中发现 ANF是该组织中上皮离子转运的有效抑制剂。 比目鱼的肠具有特征性的Na-K-Cl 共转运系统，可与袢利尿剂和 细胞内cGMP增加。 它是一个简单的，相对均匀的 上皮在其运输特性上类似于厚的上升肢 哺乳动物肾脏中的亨利氏袢。 该提案的主要目标是建立 通过ANF抑制离子转运并确定ANF样 肽作为肠离子转运的内源性调节剂， 冬比目鱼 这将需要：1）确定具体的 第二信使介导的细胞内事件负责 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)ANF样肽的鉴定和表征 比目鱼其次是比较他们的物理特性， 与哺乳动物形式的ANF的利钠和利尿活性。 结果 从这些研究应该是有用的，在了解一些细胞， 这些肽在不同组织中的潜在作用机制， 提供了一些关于离子转运如何被调节和修改的见解， 哺乳动物肾脏中的利尿剂，更具体地说， 亨利氏袢的升支

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.