MECHANISM OF RENAL ACID/BASE HOMEOSTASIS

肾酸碱平衡机制

• 批准号: 2875983
• 负责人: THOMAS D DUBOSE
• 金额: $ 5.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2875983
• 关键词: acid base balance; adenosinetriphosphatase; aldosterone; ammonia; bicarbonates; homeostasis; hydrogen potassium exchanging ATPase; 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.

肾脏对酸碱平衡的贡献很重要：1） 过滤碳酸氢盐的重吸收和2）净酸排泄。 最近的 我们实验室的研究具有阐明这两个机制 不同的过程受到调节。关于角色的新概念 铵转运，净酸的最高度调节的成分 排泄及其在酸碱稳态中的作用已经出现。 而且， 已经阐明了钾平衡对铵排泄的影响 根据我们对慢性高钾血症的研究。此外，我们探索了 并描述了多种模型中尿酸化缺陷 肾远端肾小管酸中毒。这个长期目标 拟议的一系列研究是扩展我们对 肾小管酸中毒和 高钾血症到细胞和分子水平。实现这一目标 我们将在分离的大鼠内髓中采用微灌注技术 在体外灌注导管（IMCD），并在 体内研究慢性高钾血症的影响 阻塞和慢性钒酸盐对质子分泌的施用 IMCD通过碳酸氢盐和铵转运测量。 相对 两种类型的质子的特异性抑制剂Bifilamycin和SCM 28080 泵，H+ - ATPase和H+ -K+ ATPase将用于 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收集管道以及均是IMCD 培养物中的RCCT细胞表达H+ -K+ ATPase的Messenger RNA，以及 如果该泵的表达是由酸碱和钾调节的 稳态。