PATHOPHYSIOLOGY OF CAMP AND PROSTAGLANDINS IN THE KIDNEY

肾脏中 CAMP 和前列腺素的病理生理学

• 批准号: 3227187
• 负责人: Detlef Olaf Schlondorff
• 金额: $ 26.1万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-30 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227187
• 关键词: adenylate cyclase; angiotensin II; arachidonate; cyclic AMP; cyclic nucleoside monophosphate; electron microscopy; glomerular filtration; hormone biosynthesis; hormone regulation /control mechanism; immunofluorescence technique; kidney cell; kidney disorder; kidney metabolism; lipoxygenase; membrane lipids; phospholipids; platelet activating factor; prostaglandins; protein kinase; radiotracer; renal tubular transport; tissue /cell culture; uremias; vasopressins

The proposal attempts to integrate the roles of circulating hormones and that of locally generated mediators including prostaglandins, lipoxgenase products and platelet activating factor in the function of the kidney. The questions to be examined include: 1. What is the exact mechanism by which some hormones stimulate arachidonic acid release? 2. How does this phenomenon relate to the effect of these agents on cell function? 3. Are some of the effects mediated by calcium-phospholipid-dependent protein kinase and, if so, which are the cellular substrates? 4. What is the role of lipoxygenase products on glomerular function and how is their synthesis controlled? 5. Do glomeruli and glomerular cells produce platelet activating factor, and if so is this synthesis altered in renal disease? The tissues to be studied will include: isolated glomeruli, culture of glomerular cells, toad urinary bladder, and isolated collecting tubules. The mechanism of action of vasoactive hormones, e.g. angiotensin II and vasopressin, will be examined in these tissues. Physiological parameters will include contraction of cells and transport of water and solutes. In parallel biochemical events will be determined: phospholipid turnover, arachidonic acid release, synthesis of prostaglandins and lipoxygenase products, synthesis of platelet activating factor (a lipid mediator), cAMP generation, various protein kinases and their endogenous substrates, etc. Identification of the role and mechanism of action of diverse, but interconnected lipid modulators with circulating hormones in vitro should improve our understanding of their in vivo contribution to the physiology and pathophysiology of the kidney. This knowledge will then permit the design of specific therapeutic avenues to glomerular diseases and disorders of the urinary concentrating mechanism.

该提议试图整合循环激素和 包括前列腺素，脂氧酶在内的局部产生的介体的介体 产物和血小板激活因子肾功能。 要检查的问题包括： 1。某些激素刺激蛛网膜化的确切机制是什么 酸释放？ 2。这种现象与这些药物对细胞的影响有何关系 功能？ 3。是磷脂依赖性钙介导的一些效果 蛋白激酶，如果是，哪些是细胞底物？ 4。脂氧合酶产物在肾小球功能上的作用是什么？ 它们的合成控制吗？ 5。肾小球和肾小球细胞产生血小板激活因子， 如果是这样，这种合成在肾脏疾病中会改变吗？ 要研究的组织将包括：孤立的肾小球， 肾小球细胞，蟾蜍膀胱和分离的收集小管。 血管活性激素的作用机理，例如血管紧张素II和 加压素将在这些组织中进行检查。 生理参数 将包括细胞的收缩以及水和溶质的运输。 在 将确定平行生化事件：磷脂周转率， 花生四烯酸释放，前列腺素和脂氧酶的合成 产品，血小板激活因子的合成（脂质介体），cAMP 产生，各种蛋白激酶及其内源性底物等。 识别各种作用的作用和机制，但 与循环激素的互连脂质调节剂在体外应 提高我们对他们体内生理贡献的理解 和肾脏的病理生理学。 然后，这些知识将允许 针对肾小球疾病和疾病的特定治疗途径的设计 尿液浓缩机制。