H+/HCO3- TRANSPORT BY THE COLLECTING DUCT

H /HCO3- 通过收集管运输

• 批准号: 2145048
• 负责人: I. David Weiner
• 金额: $ 6.08万
• 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 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145048
• 关键词: acid base balance; adenosinetriphosphatase; apical membrane; basolateral membrane; bicarbonates; immunocytochemistry; intracellular transport; kidney cell; laboratory rabbit; membrane transport proteins; renal tubular transport

The cortical collecting duct (CCD) plays an important role in systemic acid-base homeostasis. Recent studies show the majority of rabbit superficial CCD intercalated cells possess both apical and basolateral plasma membrane C1-/HCO3- exchange. Since this cell has both apical and basolateral C1-?HCO3-, it might be able to either secrete or reabsorb HCO3- and therefore function as either an A cell or B cell. Yet no studies have directly examined the role this cell plays to regulate CCD HCO3- transport. The central hypothesis of this application is that intercalated cell with both apical and basolateral C1-/HCO3- exchange has the capability to transport HCO3-, but that it is not active under normal conditions. When stimulated this cell may be able to either secrete or reabsorb HCO3-. This cell may play a major role in systemic acid-base physiology. Two major aims will examine this hypothesis. the first aim is to characterize the major H+ and HCO3- transporters of this cell. the presence and membrane location of Na+/H+ exchange, H+-ATPase, and H+-K+- ATPase will be determined because of the critical role they play in intracellular pH (pHi) regulation and in HCO3- transport. Apical and basolateral plasma membrane C1-/HCO3- exchange will be compared to C1- /HCO3- exchange in the A cell and B cell because this cell may represent an intermediate intercalated cell, able to function as either an A cell or B cell. The second aim will be to examine the role this cell plays to regulate CCD HCO3- transport. Studies will examine whether this cell can secrete HCO3- and whether it also can reabsorb HCO3-. Finally, we will examine whether in vivo metabolic acidosis and alkalosis induce conversion of this cell into either an A cell or B cell. These studies will measure intracellular pH in individual intercalated cells of in vitro perfused CCD to examine the location and activity of specific HCO3- and H+ transporters. Some experiments will combine this with electron microscopic examination, including immunohistochemical localization of H+-ATPase and C1-/HCO3- exchange, of the same CCD. These techniques will expand our understanding of the mechanisms by which the CCD regulates systemic acid-base homeostasis.

皮质收集管（CCD）在系统性中起重要作用 酸碱稳态。 最近的研究表明大多数兔子 浅表CCD插入的细胞具有顶端和基底外侧 质膜C1-/HCO3-交换。 因为这个细胞既有顶点又 基底外侧C1-？hco3-，它可能能够分泌或重新吸收 因此，HCO3-因此起作用A细胞或B细胞。 但是不 研究直接检查了该细胞调节CCD的作用 HCO3-运输。 该应用的中心假设是与 顶端和基底外侧C1-/HCO3-交换都具有 运输HCO3-，但在正常条件下它不活跃。 什么时候 刺激该细胞可能能够分泌或重新吸收HCO3-。 该细胞可能在全身酸基生理学中起主要作用。 两个主要目标将研究这一假设。 第一个目的是 表征该细胞的主要H+和HCO3-转运蛋白。 这 Na+/H+交换的存在和膜位置，H+-ATPase和H+-K+ - 由于它们在 细胞内pH（PHI）调节和HCO3转运。 顶 基底外侧质膜C1-/HCO3-将与C1-进行比较 /hco3-在A单元和B单元中交换，因为该单元可能代表 中间插入的单元，能够用作A单元 或B单元。 第二个目的是检查该单元的调节作用 CCD HCO3-运输。 研究将检查该细胞是否可以分泌 HCO3-以及是否也可以重新吸收HCO3-。 最后，我们将检查 体内代谢性酸中毒和碱性病是否诱导 该细胞进入A细胞或B细胞。 这些研究将测量个体插入的细胞内pH 体外灌注CCD的细胞检查 特定的HCO3和H+转运蛋白。 一些实验将结合起来 通过电子显微镜检查，包括免疫组织化学 同一CCD的H+-ATPase和C1-/HCO3-交换的定位。 这些 技术将扩展我们对我们对机制的理解 CCD调节全身酸基稳态。