H/HCO3 TRANSPORT BY THE COLLECTING DUCT

通过收集管输送 H/HCO3

• 批准号: 6653663
• 负责人: I. David Weiner
• 金额: $ 2.54万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653663
• 关键词: acid base balance; ammonia; apical membrane; basolateral membrane; bicarbonates; calcium; calmodulin; genetically modified animals; immunocytochemistry; intracellular transport; kidney cell; laboratory mouse; laboratory rabbit; membrane transport proteins; mitogen activated protein kinase; perfusion; potassium; renal tubular transport; secretion

Ammonia plays a central role in acid-base homeostasis. It is produced by the proximal tubule, concentrated in the renal interstitium by the loop of Henle and excreted into the urine in the collecting duct. The production and excretion of ammonia results in equimolar production of new bicarbonate molecules, thereby allowing ammoniagenesis and excretion to contribute to acid-base homeostasis. Recent studies show that ammonia has additional functions that are completely independent of its role as a urinary constituent. These studies show that ammonia stimulates CCD net bicarbonate reabsorption through stimulation of H,K-ATPase. Thus, the increased ammonia that results from metabolic acidosis and hypokalemia may result in feedback stimulation of H,K-ATPase-mediated proton secretion and potassium reabsorption. The purpose of the proposed studies is to increase our understanding of the mechanisms through which ammonia increases CCD net bicarbonate reabsorption. The Specific Aims through which these plans will pursue this overall goal are: 1) to define the specific transporters regulated by ammonia that effect the changes in proton secretion and net bicarbonate reabsorption; 2) to define the basic signaling mechanisms through which ammonia regulates these transporters, with specific emphasis on the calcium-calmodulin, MAPK and microtubule-dependent pathways; and, 3) to define whether the chronic effects of ammonia are related to stimulation of protein expression or through inhibition of cathepsin-mediated protein degradation.

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