ROLE OF C-AMP IN RENIN RELEASE

C-AMP 在肾素释放中的作用

• 批准号: 3088305
• 负责人: WINFRED D MAGEE
• 金额: $ 6.69万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-06-01 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3088305
• 关键词: adenosine; adenylate cyclase; baroreceptors; beta adrenergic receptor; cyclic AMP; isoproterenol; juxtaglomerular apparatus; kidney metabolism; laboratory rat; phosphodiesterase inhibitors; prostaglandins; protein kinase; radioimmunoassay; renin; secretion; theophylline; tissue /cell culture

In vivo studies indicate that renin release is controlled by three intrarenal mechanisms-the baroreceptor, macula densa and beta-adrenoreceptors. Much evidence supports the concept that prostaglandin I2 serves as extracellular mediator linking activation of baroreceptor or macula densa to renin release by juxtaglomerular cells. Similarly, norepinephrine serves as extracellular mediator linking activation of beta adrenoreceptor to renin release by juxtaglomerular cells. Since both prostaglandin I2 and beta adrenoreceptor agonists can stimulate release of renin by juxtaglomerular cells, and since adenosine is inhibitory, we propose that cyclic adenosine monophosphate serves as the intracellular mediator. The use of a number of substances which either stimulate or inhibit renin and cyclic adenosine monophosphate production in juxtaglomerular cells (eg. prostaglandin I2, isoproterenol, 9-substituted adenosine derivatives, phosphodiesterase inhibitors, protein kinase inhibitors) will be used to test our hypothesis. Data on renin release and cyclic adenosine monophosphate production as determined by radioimmunoassay on a cell culture system enriched in juxtaglomerular cells will be evaluated.

体内研究表明，肾素的释放受三个因素的控制， 肾内机制-压力感受器，致密斑和 β-肾上腺素受体 许多证据支持这样一个概念， 前列腺素I2作为细胞外介质， 压力感受器或致密斑对肾小球细胞释放肾素的影响。 同样，去甲肾上腺素作为细胞外介质连接 β-肾上腺素受体对肾小球肾素释放的激活作用 细胞 由于前列腺素I2和β肾上腺素受体激动剂都可以 刺激肾小球细胞释放肾素，由于腺苷是 抑制，我们建议，环磷酸腺苷作为 胞内介质 使用一些刺激或抑制肾素的物质 和肾小球细胞中环腺苷酸的产生（例如， 前列腺素I2，异丙肾上腺素，9-取代的腺苷衍生物， 磷酸二酯酶抑制剂、蛋白激酶抑制剂）将用于 验证我们的假设 关于肾素释放和环腺苷的数据 通过放射免疫测定法测定细胞上的单磷酸盐产生 将评价富含肾小球细胞的培养系统。