AE2 CI/HCO3 Exchanger and Transepithelial Ion Transport

AE2 CI/HCO3 交换器和跨上皮离子传输

• 批准号: 7054665
• 负责人: Lara R Gawenis
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054665
• 关键词: acidity /alkalinity; bicarbonates; bile; chloride ion; colon; diarrhea; gastrointestinal absorption /transport; gastrointestinal epithelium; gene expression; gene targeting; genetically modified animals; intestinal villi; ion transport; laboratory mouse; membrane activity; membrane channels; polymerase chain reaction; postdoctoral investigator; sodium ion

DESCRIPTION (provided by applicant): The overall goal of this research is to determine the physiological role of the AE2 anion exchanger in epithelial cells that line the colon and biliary system. AE2 functions to exchange one chloride for one bicarbonate ion across the membrane of many cell types. This activity results in net chloride movement into the cell (where it is available for secretion by other transporters) and net bicarbonate movement out of the cell. In the colon, AE2 has been proposed to mediate chloride uptake into the epithelial cells to support transepithelial secretion and to provide an exit pathway for bicarbonate from the cell during bicarbonate absorption. In the biliary system, AE2 is believed to be expressed on the apical membrane and mediate the electrically-silent component of bicarbonate secretion into bile. Using gene-targeting technology, the aims of this proposal are i) to test the hypotheses that AE2 is critical to chloride and bicarbonate transport in colonic and biliary epithelial cells and 2) develop an intestine-specific AE2 knockout to evaluate the role of AE2 in colonic bicarbonate absorption.

描述（由申请人提供）：本研究的总体目标是确定AE2阴离子交换剂在结肠和胆道系统上皮细胞中的生理作用。AE2的功能是在许多细胞类型的膜上将一个氯离子交换为一个碳酸氢根离子。该活性导致净氯离子移动到细胞中（在那里它可用于由其他转运蛋白分泌）和净碳酸氢盐移动到细胞外。在结肠中，已提出AE2介导氯化物摄取到上皮细胞中以支持跨上皮分泌，并在碳酸氢盐吸收期间提供碳酸氢盐从细胞的排出途径。在胆道系统中，AE2被认为在顶膜上表达，并介导碳酸氢盐分泌到胆汁中的电沉默组分。使用基因靶向技术，本提案的目的是i）检验AE2对结肠和胆管上皮细胞中的氯离子和碳酸氢盐转运至关重要的假设，2）开发一种精氨酸特异性AE2敲除，以评价AE2在结肠碳酸氢盐吸收中的作用。