MECHANISM OF RENAL ACID/BASE HOMEOSTASIS

肾酸碱平衡机制

• 批准号: 2138411
• 负责人: THOMAS D DUBOSE
• 金额: $ 20.05万
• 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/2138411
• 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） 重吸收过滤的碳酸氢盐和2）净酸排泄。 最近 我们实验室的研究已经阐明了这两种 不同的过程受到监管。关于联合国作用的新概念 铵转运，净酸中调节最高的组分 排泄，以及它在酸碱平衡中的作用已经出现。 此外，委员会认为， 阐明了钾平衡对铵排泄的影响 从我们对慢性高钾血症的研究中。此外，我们还探索了 并描述了各种模型中尿酸化的缺陷 远端肾小管酸中毒这一长期目标 建议的一系列研究是扩大我们的检查， 肾小管性酸中毒中酸化缺陷的病理生理学， 高钾血症的细胞和分子水平。完成这一目标 我们将采用微灌注技术在离体大鼠内髓 收集管（IMCD）在体外灌注，乳头状微穿刺， 探讨体内慢性高钾血症对输尿管的影响 阻塞和慢性钒酸盐给药对质子分泌的影响 通过碳酸氢盐和铵转运测定IMCD。 相对 特异性抑制剂，bifilamycin和SCM 28080，两种类型的质子 泵、H+ -ATP酶和H+ -K+ ATP酶将分别用于 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 培养的RCCT细胞表达H+ -K+ ATP酶的信使RNA， 如果该泵的表达受酸碱和钾调节 体内平衡