H/HCO3 TRANSPORT BY THE COLLECTING DUCT

氨在酸碱平衡中起着核心作用。它是 由近端小管产生，集中在肾间质中由 亨勒环，排泄到集合管的尿液中。这个 氨的产生和排泄导致等摩尔的新的 碳酸氢盐分子，从而允许氨化和排泄 有助于酸碱平衡。最近的研究表明，氨具有 附加功能完全独立于其作为尿路的角色 选民。这些研究表明，氨刺激了CCD型净碳酸氢盐 通过刺激H，K-ATPase重吸收。因此，增加的氨 代谢性酸中毒和低钾血症可能会导致反馈 H，K-ATPase介导的质子分泌和钾重吸收的刺激。 建议进行研究的目的是加深我们对 氨促进小苏打净重吸收的机制。 这些计划实现这一总体目标的具体目标是： 1)定义受氨调节的特定转运体，从而影响 质子分泌和碳酸氢盐净重吸收的变化；2)定义 氨调节这些转运体的基本信号机制， 特别强调钙-钙调蛋白、MAPK和 微管依赖的通路；以及，3)确定慢性效应 氨的含量与蛋白质表达的刺激或通过 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.