REGULATION OF URINARY ACIDIFICATION

尿液酸化的调节

• 批准号: 3234540
• 负责人: NEIL A KURTZMAN
• 金额: $ 15.05万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234540
• 关键词: acetazolamide; acid base balance; acidity /alkalinity; adenosine triphosphate; aldosterone; alkalosis; amiloride; ammonia; bicarbonates; biological fluid transport; body fluid balance therapy; calcium disorder; chronic disease /disorder; controlled environment chamber; dietary mineral; dietary trace element; hypercapnia; hyperparathyroidism; intracellular; ion transport; kidney pharmacology; lithium; longitudinal animal study; membrane permeability; micropuncture; mineralocorticoids; nuclear magnetic resonance spectroscopy; nutrient interaction; nutrition related tag; parathyroid hormones; parathyroidectomy; phosphates; phosphorus metabolism disorders; renal failure; renal tubular transport; renal tubule; respiratory acidosis; urinary bladder; urine acidity; vanadium

The studies proposed in this application are divided into three sections depending on the technique used. They are all designed to answer fundamental questions concerning the physiology and pathophysiology of distal urinary acidification. The first set of studies uses clearance techniques and will attempt to use the ability to lower the urine pC02 as an index of distal acidification. We believe that the titration of nonbicarbonate buffer consumes C02 and in the absence of bicarbonate buffer lowers the final urine pC02 to a value below that of blood. We also believe that this consumption of C02 can be disclosed in the presence of urinary bicarbonate by the simultaneous infusion of carbonic anhydrase. These studies will also examine the role of aldosterone on both cortical and medullary collecting duct acidification. The second group of studies uses the turtle bladder as a probe. It will attempt to examine the role of transepithelial voltage on carbonic anhydrase-independent acidification in this membrane. We will also attempt to dissect the different transport properties of the granular and mitochondrial rich cells in this membrane. The relationship of voltage to the backleak produced by the antifungal antibiotic amphotericin B will be examined, as will the effect of amiloride on bicarbonate permeability. Finally, the effect of vanadate, a well known inhibitor of proton secretion, on bicarbonate secretion will be examined. The third section of these studies deals with the role of proton ATPase in collecting duct acidification. These studies will test the hypothesis that proton ATPase can be measured in the mammalian collecting tubule and that its activity correlates with the state of acidification in this nephron segment. These studies will make use of the technique of enzyme analysis in in vitro nephron fragments. Taken as a whole, these studies are designed to continue our long-term examination of the forces which control distal urinary acidification under normal and abnormal circumstances.

本申请中提出的研究分为三个部分 取决于所使用的技术。 它们都是为了回答 有关生理学和病理生理学的基本问题 远端尿液酸化。 第一组研究使用间隙 技术，并将尝试利用降低尿液 pCO2 的能力 远端酸化指数。 我们认为滴定 非碳酸氢盐缓冲液消耗CO2并且在没有碳酸氢盐缓冲液的情况下 将最终尿液 pCO2 降低至低于血液的值。 我们也 相信可以在有以下人员在场的情况下披露这一二氧化碳消耗量： 通过同时输注碳酸酐酶而产生尿碳酸氢盐。 这些研究还将检查醛固酮对皮质和大脑皮层的作用。 和髓质集合管酸化。 第二组研究 使用海龟膀胱作为探针。 它将尝试检查的作用 跨上皮电压对碳酸酐酶独立酸化的影响 这个膜。 我们还将尝试剖析不同的运输 该膜中富含颗粒和线粒体的细胞的特性。 电压与抗真菌剂产生的回漏的关系 将检查抗生素两性霉素 B 以及阿米洛利的效果 关于碳酸氢盐渗透性。 最后，众所周知的钒酸盐的作用 将检查质子分泌抑制剂对碳酸氢盐分泌的影响。 这些研究的第三部分涉及质子 ATP 酶在 集合管酸化。 这些研究将检验以下假设： 质子 ATP 酶可以在哺乳动物集合管中测量，并且 其活性与肾单位的酸化状态相关 部分。 这些研究将利用酶分析技术 体外肾单位片段。 总的来说，这些研究是 旨在继续我们对控制力量的长期审查 正常和异常情况下远端尿液酸化。