H/HCO3 transport in the collecting duct

H/HCO3 在集合管中的运输

• 批准号: 7069503
• 负责人: I. David Weiner
• 金额: $ 25.75万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7069503
• 关键词: acidosis; ammonia; blood groups; cell line; glycoproteins; hypokalemia; intracellular transport; ion transport; kidney function; kidney metabolism; laboratory mouse; phosphorylation; protein quantitation /detection; renal tubular transport; renal tubule; transport proteins

DESCRIPTION (provided by applicant): Ammonia metabolism is critical for normal health. Inappropriate ammonia metabolism in the kidney leads to metabolic acidosis and in the liver leads to ammonia encephalopathy. In the central nervous system increased extracellular ammonia alters neuronal function and can lead to encephalopathy. Accordingly, understanding the cellular and molecular mechanisms of ammonia metabolism, which includes ammonia transport, is important. Recent studies have identified a novel family of ammonium ion (NH4+)-specific transporters. These proteins were first identified in yeast and in plants, and homologues are present throughout nature. In model systems, such as yeast, plants and bacteria, these are intrinsic membrane proteins that mediate high-affinity, ammonium-specific transport and whose expression is physiologically regulated. Two of these proteins, RhBG and RhCG are expressed in the connecting segment and the collecting duct of the kidney, and exhibit polarized expression. These observations lead us to postulate that RhBG and RhCG are integral membrane, physiologically-regulated ammonium-ion transporters that play critical roles in renal ammonia metabolism. The broad, long-term objectives of this project are to define the roles of RhBG and RhCG in mammalian renal physiology. To do so, the Specific Aims of the current proposal are to: (1) Define the regulation of mouse renal RhBG and RhCG expression and vesicular trafficking in response to specific clinical conditions associated with altered renal ammonia metabolism; (2) Determine the mechanism of extracellular ammonia-stimulated changes in RhBG- and RhCG-mediated ion transport; and, (3) identify the specific ion-transport characteristics of RhBG and RhCG. We will utilize in vivo animal models of altered renal ammonia metabolism, metabolic acidosis and alkalosis and hypokalemia, to define the regulation of RhBG and RhCG expression and cellular localization, a cultured collecting duct cell line, mIMCD-3, for in vitro studies examining the cellular mechanisms underlying regulation of RhBG and RhCG-mediated transport, and heterologous expression systems in which to define the specific ion transport characteristics of RhBG and RhCG.

描述（由申请人提供）：氨代谢对于正常健康至关重要。肾脏中不适当的氨代谢会导致代谢性酸中毒和肝脏导致氨脑病。在中枢神经系统中，细胞外氨们会改变神经元功能，并可能导致脑病。因此，了解氨代谢的细胞和分子机制（包括氨转运）很重要。最近的研究已经确定了一种新型的铵离子（NH4+） - 特定转运蛋白家族。这些蛋白质首先在酵母和植物中鉴定出来，同源物在整个自然界中存在。在诸如酵母，植物和细菌之类的模型系统中，它们是介导高亲和力，特异性转运且其表达在生理上调节的固有膜蛋白。这些蛋白中的两种，RHBG和RHCG在肾脏的连接段和收集管中表达，并表现出偏振表达。这些观察结果使我们假设RHBG和RHCG是整体膜，生理调节的铵离子转运蛋白，它们在肾氨代谢中起关键作用。该项目的广泛长期目标是定义RHBG和RHCG在哺乳动物肾脏生理学中的作用。为此，当前建议的具体目的是：（1）定义小鼠肾脏RHBG和RHCG表达和囊泡运输的调节，以响应与肾氨代谢改变相关的特定临床条件； （2）确定RHBG和RHCG介导的离子转运的细胞外氨刺激变化的机制； （3）确定RHBG和RHCG的特定离子传输特性。 We will utilize in vivo animal models of altered renal ammonia metabolism, metabolic acidosis and alkalosis and hypokalemia, to define the regulation of RhBG and RhCG expression and cellular localization, a cultured collecting duct cell line, mIMCD-3, for in vitro studies examining the cellular mechanisms underlying regulation of RhBG and RhCG-mediated transport, and heterologous expression systems in定义RHBG和RHCG的特定离子传输特性。