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: 3227190
• 负责人: Detlef Olaf Schlondorff
• 金额: $ 27.74万
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227190
• 关键词: Anura; adenylate cyclase; angiotensin II; arachidonate; calmodulin; cyclic AMP; cyclic nucleoside monophosphate; electron microscopy; glomerular filtration; hormone biosynthesis; hormone regulation /control mechanism; immunofluorescence technique; kidney cell; kidney disorder; kidney metabolism; laboratory rabbit; laboratory rat; 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.

该提案试图整合循环激素和 局部产生的介质，包括前列腺素、脂氧合酶 产品和血小板激活因子对肾脏的功能。 需要审查的问题包括： 1. 某些激素刺激花生四烯酸的确切机制是什么 酸释放？ 2. 这种现象与这些药物对细胞的作用有何关系 功能？ 3. 一些效应是由钙磷脂依赖性介导的吗？ 蛋白激酶，如果是的话，哪些是细胞底物？ 4. 脂氧合酶产品对肾小球功能有何作用以及如何作用 它们的合成受到控制吗？ 5、肾小球和肾小球细胞产生血小板活化因子吗？ 如果是的话，这种合成在肾脏疾病中是否会改变？ 要研究的组织包括：分离的肾小球、培养物 肾小球细胞、蟾蜍膀胱和分离的集合管。 血管活性激素的作用机制，例如血管紧张素II和 将在这些组织中检查加压素。 生理参数 将包括细胞的收缩以及水和溶质的运输。 在 将确定平行的生化事件：磷脂周转， 花生四烯酸的释放、前列腺素和脂氧合酶的合成 产品，血小板激活因子（脂质介质）的合成，cAMP 生成、各种蛋白激酶及其内源底物等。 作用和作用机制鉴定多样，但 体外循环激素与脂质调节剂相互关联 提高我们对它们在体内对生理学贡献的理解 和肾脏的病理生理学。 这些知识将允许 肾小球疾病和病症的具体治疗途径的设计 尿液浓缩机制。