SODIUM ENTRY INTO AMILORIDE-SENSITIVE EPITHELIA

建议的研究是为了阐明易化的分子基础。 外膜(或根尖膜)中存在的钠内流机制 紧密的上皮组织。这一钠进入步骤是以下步骤的重要组成部分 负责盐和盐净流动的整个主动运输系统 水穿过这些建筑物。这个进入过程是被动的，而且是敏感的 利尿剂阿米洛利的抑制作用。其作用机理分析。 NA条目包括阳离子选择性的测定， 钠上的化学基团特异性试剂和其他药理物质 进入和阿米洛利效率，结合位点数量的确定 光敏阿米洛利类似物(溴阿米洛利)的研究 含功能性钠离子进入位点的膜囊的制备。一个 比较方法：利用两栖动物皮肤和膀胱 准备工作以及离体兔结肠。这些研究 将有助于我们了解它的动力学和生化性质 上皮性转运系统，增加我们对其模式的理解 阿米洛利和其他利尿剂的作用。

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.