H/HCO3 TRANSPORT BY THE COLLECTING DUCT

通过收集管输送 H/HCO3

• 批准号: 6380757
• 负责人: I. David Weiner
• 金额: $ 21.75万
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380757
• 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.

氨在酸碱平衡中起着核心作用。这是 由近端小管产生，集中于肾间质 亨利氏袢（Henle Loop）并通过集合管排泄到尿液中。这 氨的产生和排泄导致新的等摩尔产生 碳酸氢盐分子，从而允许氨的生成和排泄 有助于酸碱平衡。最近的研究表明，氨具有 完全独立于其作为泌尿系统的作用的附加功能 组分。这些研究表明氨会刺激 CCD 净碳酸氢盐 通过刺激 H,K-ATP 酶进行重吸收。因此，增加的氨 由代谢性酸中毒和低钾血症引起的可能会导致反馈 刺激 H,K-ATP 酶介导的质子分泌和钾重吸收。 拟议研究的目的是增加我们对 氨增加 CCD 净碳酸氢盐重吸收的机制。 这些计划实现这一总体目标的具体目标是： 1) 定义受氨调节的、影响 质子分泌和净碳酸氢盐重吸收的变化； 2）定义 氨调节这些转运蛋白的基本信号机制， 特别强调钙-钙调蛋白、MAPK 和 微管依赖性途径； 3) 定义是否存在慢性影响 氨的增加与蛋白质表达的刺激有关或通过 抑制组织蛋白酶介导的蛋白质降解。