H/HCO3 TRANSPORT BY THE COLLECTING DUCT

氨在酸碱平衡中起着核心作用。是 由近端小管产生，通过 Henle袢并在集合管中排泄到尿液中。的 氨的产生和排泄导致等摩尔的新的 碳酸氢盐分子，从而允许氨生成和排泄， 有助于酸碱平衡最近的研究表明，氨具有 其他功能完全独立于其作为泌尿系统的作用， 选民这些研究表明，氨刺激CCD净碳酸氢盐 通过刺激H，K-ATP酶的重吸收。因此，增加的氨 由代谢性酸中毒和低钾血症引起的， 刺激H，K-ATP酶介导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净重吸收的机制。 这些计划旨在实现这一总体目标的具体目标是： 1)以确定由氨调节的特定转运蛋白， 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;和，3）以确定是否慢性效应 氨与蛋白质表达的刺激有关， 抑制组织蛋白酶介导的蛋白质降解。

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.