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The investigation of molecular biological mechanisms and therapy of refractory renal edema.

难治性肾水肿的分子生物学机制及治疗研究。

基本信息

批准号：
08671291
负责人：
NONOGUCHI Hiroshi
金额：
$ 1.41万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671291/
关键词：
edema vasopressin V1a receptor V2 receptor mRNA collecting duct 脱水プロスタグラデイン E2 V1a受容体 V2受容体 competitive PCR プロスタグランディン E2 集合尿細管杭利尿ホルモン慢性腎不全 RT-PCR

项目摘要

This study was designed to investigate the mechanisms and therapy of refractory renal edema. We have focused on V1a and V2 vasopressin (ADH) receptors. WE have already reported the V2 receptor is localized in basolateral membrane of distal nephron segments. Therefore, we first investigated intranephron localization of V1a receptor. The results showed that V1a receptor is located in glomeruli and in luminal membrane of collecting ducts.Next, the mechanisms of V2 receptor (V2R) mRNA expression in inner medullary collecting ducts (IMCD) were investigated. V2R mRNA is known to downregulate in dehydration. However, vasopressin and hyperosmolality, both are known to increase in dehydration, stimulated V2R mRNA expression in vitro. There is some inhibitory factor on V2R mRNA expression in dehydration. One of the canditate is prostaglandin E2 (PGE2). PGE2 is known to decrease ADH-dependent cAMP generation in collecting ducts. PGE2 inhibited ADH- and hyperosmolality-stimulated V2R mRNA expression. Thus, increased PGE2 generation seems to inhibit V2R mRNA expression in dehydration. We are still investigating the role of PGE2 to know the mechanisms of diuresis. The final goal of our study is to use our knowledge for the therapy of renal edema.

本研究旨在探讨难治性肾水肿的发病机制和治疗方法。我们重点关注V1a和V2加压素（ADH）受体。我们已经报道V2受体定位于远端肾单位的基底膜。因此，我们首先研究了V1a受体的肾内定位。结果表明，V1a受体定位于肾小球和集合管的管腔膜，并探讨了V2受体（V2R）mRNA在内髓集合管（IMCD）中的表达机制。已知V2R mRNA在脱水中下调。然而，加压素和高渗透压，都是已知的增加脱水，刺激V2R mRNA的表达在体外。脱水时V2R mRNA的表达存在一定的抑制因素。前列腺素E2（PGE2）是其中一种。已知PGE2减少集合管中ADH依赖性cAMP的产生。PGE 2抑制抗利尿激素和高渗透压刺激的V2 R mRNA表达。因此，增加的PGE2产生似乎抑制脱水中V2R mRNA的表达。我们仍在研究PGE 2的作用，以了解利尿的机制。本研究的最终目的是将我们的知识用于肾水肿的治疗。