SODIUM ENTRY INTO AMILORIDE-SENSITIVE EPITHELIA

钠进入阿米洛利敏感上皮细胞

• 批准号: 3235974
• 负责人: DALE J BENOS
• 金额: $ 11.49万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3235974
• 关键词: adenosinetriphosphatase; amiloride; cations; epithelium; gastrointestinal epithelium; ligands; membrane permeability; nitrene; passive transport; radiotracer; sodium

The proposed research is to elucidate the molecular basis of the facilitated sodium entry mechanism which exists in the outer (or apical) membrane of all tight epithelial tissues. This sodium entry step is an essential component of the overall active transport system responsible for the net movement of salt and water across these structures. This entry process is passive, and is sensitive to inhibition by the diuretic drug, amiloride. The analysis of the mechanism of Na entry encompasses determinations of cation selectivities, the effects of chemical group-specific reagents and other pharmacological substances on Na entry and amiloride efficiency, a determination of site number from binding studies of a photosensitive amiloride analogue (bromoamiloride), and the preparation of membrane vesicles containing functional Na-entry sites. A comparative approach, utilizing the isolated amphibian skin and bladder preparations as well as the isolated rabbit colon, will be taken. These studies will contribute to our knowledge of the kinetic and biochemical properties of epithelial transport systems and increase our comprehension of the mode of action of amiloride and other diuretic compounds.

这项研究的目的是阐明易化蛋白的分子基础， 钠进入机制，存在于所有的外（或顶端）膜 紧密的上皮组织。 这个钠进入步骤是一个重要组成部分， 负责盐净运动的整个主动运输系统， 水流过这些结构。 这个进入过程是被动的，而且是敏感的 利尿药阿米洛利的抑制作用 机理分析 Na进入包括阳离子选择性的测定， 化学基团特异性试剂和其他药理学物质对Na 进入和阿米洛利效率，结合位点数的测定 光敏阿米洛利类似物（溴阿米洛利）的研究， 制备含有功能性Na-进入位点的膜囊泡。 一 比较方法，利用离体两栖动物皮肤和膀胱 制备物以及分离的兔结肠。 这些研究 将有助于我们了解的动力学和生物化学性质， 上皮运输系统，并增加我们的理解模式， 阿米洛利和其他利尿化合物的作用。