MECHANISM OF RENAL ACID/BASE HOMEOSTASIS

肾酸碱平衡机制

• 批准号: 2138413
• 负责人: THOMAS D DUBOSE
• 金额: $ 21.42万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2138413
• 关键词: acid base balance; adenosinetriphosphatase; aldosterone; ammonia; bicarbonates; homeostasis; hydrogen transport; hyperkalemias; isolation perfusion; laboratory rat; messenger RNA; micropuncture; renal tubule acidosis; tissue /cell culture; ureter obstruction

The kidney contributes importantly to acid-base balance by: 1) reabsorption of filtered bicarbonate and by 2) net acid excretion. Recent studies in our laboratory have elucidated mechanisms by which these two distinct processes are regulated. New concepts regarding the role of ammonium transport, the most highly regulated component of net acid excretion, and its role in acid-base homeostasis have emerged. Moreover, the impact of potassium balance on ammonium excretion has been elucidated from our studies of chronic hyperkalemia. In addition, we have explored and described defects in urinary acidification in a wide variety of models of distal renal tubular acidosis. The long term objectives of this proposed series of studies is to extend our examination of the pathophysiology of the acidification defects in renal tubular acidosis and hyperkalemia to the cellular and molecular level. To accomplish this goal we will employ microperfusion techniques in isolated rat inner medullary collecting ducts (IMCD) perfused in vitro, and papillary micropuncture in vivo to investigate the impact of chronic hyperkalemia, ureteral obstruction and chronic vanadate administration on proton secretion by the IMCD as measured by bicarbonate and ammonium transport. The relatively specific inhibitors, bifilamycin and SCM 28080, of the two types of proton pumps, H+ - ATPase, and H+ -K+ ATPase, respectively, will be used to determine the role of these pumps in defects of acidification. Secondly, we will determine if cortical and medullary collecting ducts and both IMCD and RCCT cells in culture express messenger RNA for the H+ -K+ ATPase, and if expression of this pump is modulated by acid base and potassium homeostasis.

肾脏通过以下方式对酸碱平衡做出重要贡献：1) 过滤后的碳酸氢盐的重吸收和2)净酸排泄。 最近的 我们实验室的研究已经阐明了这两种机制 不同的流程受到监管。关于角色的新概念 铵运输，净酸中监管最严格的组成部分 排泄及其在酸碱平衡中的作用已经出现。 而且， 钾平衡对铵排泄的影响已被阐明 来自我们对慢性高钾血症的研究。此外，我们还探索了 并描述了多种模型中尿液酸化的缺陷 远端肾小管酸中毒。本次活动的长期目标 拟议的一系列研究是为了扩展我们对 肾小管性酸中毒酸化缺陷的病理生理学 高钾血症达到细胞和分子水平。为了实现这个目标 我们将在离体大鼠内髓中采用微灌注技术 集合管（IMCD）体外灌注，乳头微穿刺 体内研究慢性高钾血症、输尿管 阻塞和长期施用钒酸盐对质子分泌的影响 IMCD 通过碳酸氢根和铵传输来测量。 相对而言 两种质子的特异性抑制剂双丝霉素和 SCM 28080 泵、H+ - ATPase 和 H+ -K+ ATPase 分别用于 确定这些泵在酸化缺陷中的作用。第二， 我们将确定皮质和髓质集合管以及 IMCD 是否 培养的 RCCT 细胞表达 H+ -K+ ATP 酶的信使 RNA，并且 如果该泵的表达受到酸碱和钾的调节 体内平衡。