H/HCO3 transport in the collecting duct

H/HCO3 在集合管中的运输

• 批准号: 8068328
• 负责人: I. David Weiner
• 金额: $ 28.61万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068328
• 关键词: Acids; Adult; Alkalosis; Ammonia; Apical; Bicarbonates; Cell membrane; Cells; Characteristics; Child; Dietary Potassium; Disease; Duct (organ) structure; Excretory function; Family member; Gene Deletion; Glycoproteins; Goals; Growth; Growth Disorders; H(+)-K(+)-Exchanging ATPase; HSV glycoprotein C; Health; Homeostasis; Hypokalemia; Intercalated Cell; Ion Transport; Kidney; Kidney Calculi; Lead; Mediating; Metabolic; Metabolic acidosis; Metabolism; Modeling; Morbidity - disease rate; Movement; Mus; Muscular Atrophy; Nephrolithiasis; Osteoporosis; Physiological; Potassium; Potassium Deficiency; Proton-Translocating ATPases; Regulation; Role; Skeletal Muscle; Technology; Time; Transgenic Mice; Work; apical membrane; base; cell type; disorder prevention; insight; novel; public health relevance; response; skeletal disorder; urinary

DESCRIPTION (provided by applicant): A major advance in our understanding of acid-base homeostasis and ammonia metabolism is the identification that Rh glycoproteins are ammonia transporters. In the kidney, multiple lines of evidence suggest that Rh glycoprotein C Glycoprotein (Rhcg) is critically important in renal ammonia metabolism. A second advance has been the recognition that Rhcg is expressed in principal cells, a cell not generally known to be involved in acid-base homeostasis, and that principal cell Rhcg expression parallels ammonia excretion. Thus, principal cells may contribute to regulated transcellular ammonia secretion. Finally, Rhcg expression appears to be regulated through post-transcriptional mechanisms. The overall aim of this application is to determine Rhcg's role in acid-base homeostasis and in potassium homeostasis. The first goal is to determine the specific role of Rhcg in the renal response to metabolic acidosis. We will use Cre-loxP technology to generate transgenic mice with kidney-specific, intercalated cell-specific and principal cell-specific Rhcg deletion. We will then examine acid- base homeostasis in these mice under control conditions and in response to metabolic acidosis in order to determine the specific role of Rhcg in renal acid-base homeostasis, and the specific contributions of intercalated cells and principal cells to acid-base homeostasis. Our second aim is to determine Rhcg's specific role in the renal response to hypokalemia. We will again use Cre-loxP technology to generate transgenic mice with kidney- specific, intercalated cell-specific and principal cell-specific Rhcg deletion. We will then examine acid-base and potassium homeostasis in these mice under control conditions and in response to dietary potassium deficiency in order to determine the specific role of Rhcg in the renal response to hypokalemia, and the specific contributions of intercalated cells and principal cells to Rhcg-mediated ion transport in response to hypokalemia. PUBLIC HEALTH RELEVANCE Acid-base disorders are associated with renal stone disease, osteoporosis, muscle atrophy, growth retardation and increased morbidity. The proposed studies will provide new insights into the fundamental mechanisms of acid-base homeostasis, thereby providing underpinnings for new and novel treatments.

描述（由申请人提供）：我们对酸碱平衡和氨代谢的理解的一个重大进展是Rh糖蛋白是氨转运蛋白的鉴定。在肾脏中，多条证据表明Rh糖蛋白C糖蛋白（Rhcg）在肾氨代谢中至关重要。第二个进展是认识到Rhcg在主细胞中表达，通常不知道该细胞参与酸碱平衡，并且主细胞Rhcg表达与氨排泄平行。因此，主细胞可能有助于调节跨细胞氨分泌。最后，Rhcg的表达似乎是通过转录后机制调节的。本申请的总体目的是确定Rhcg在酸碱平衡和钾平衡中的作用。第一个目标是确定Rhcg在代谢性酸中毒的肾脏反应中的具体作用。我们将使用Cre-loxP技术产生具有肾脏特异性、嵌入细胞特异性和主细胞特异性Rhcg缺失的转基因小鼠。然后，我们将在对照条件下和代谢性酸中毒反应中检查这些小鼠的酸碱平衡，以确定Rhcg在肾酸碱平衡中的具体作用，以及闰细胞和主细胞对酸碱平衡的具体贡献。我们的第二个目的是确定Rhcg在低钾血症的肾脏反应中的具体作用。我们将再次使用Cre-loxP技术来产生具有肾特异性、嵌入细胞特异性和主细胞特异性Rhcg缺失的转基因小鼠。然后，我们将检查酸碱和钾稳态在这些小鼠在控制条件下，并在饮食中钾缺乏，以确定具体的作用，Rhcg在肾脏对低钾血症的反应，和具体的贡献的嵌入细胞和主细胞Rhcg介导的离子转运在低钾血症。 公共卫生相关性 酸碱平衡紊乱与肾结石病、骨质疏松症、肌肉萎缩、生长迟缓和发病率增加有关。拟议的研究将为酸碱平衡的基本机制提供新的见解，从而为新的和新颖的治疗提供基础。