INTRACELLULAR REACTIONS IN GASTRIC MUCOSA

该项目的长期目标是确定和描述 作为盐酸分泌基础的细胞内反应 通过胃壁细胞。胃酸分泌起着重要的作用 在消化过程中的作用，它是一个主要的促进因素 消化性溃疡和反流性食管炎。关于如何胃部的信息 因此，酸的分泌是受调节的，这将有助于 胃肠生理学及对临床的处理 胃肠道疾病。 这项提案的具体目标将寻求研究下列机制 导致胃H-K-ATPase的激活，已知该酶负责 通过这种组织进行的质子运输。其中一组研究旨在 建立了一种定量的激活和失活的动力学模型 完整的壁细胞中的质子泵。这些研究将采用 最新发展的H-K-ATPase活性原位测定方法 估计与酸分泌有关的活性质子泵的数量 费率。稳态下有效质子泵个数的测量 在分泌物开始或恢复的条件下，将用于 构建了主动泵周转率的定量模型。结果将会是 用来检验胃酸分泌是由 H-K-ATPase在活性和非活性之间的分布。第二盘 将使用胃膜囊泡来表征两个 传输过程、氯离子电导和阳离子交换器，其 最近被鉴定为与H-K存在于同一膜中 ATPase。这些研究将提供有关这些问题的性质的信息 过程及其在调节H-K活性中的可能作用 ATPase。此外，由于几个项目使用了奥美拉唑，一种新的 抗溃疡药物，将获得有关作用机制的信息 对于理解临床上的这种化合物可能很重要 这种新的治疗剂的作用。

The long-term goal of this project is to identify and characterize the intracellular reactions which underlie the secretion of hydrochloric acid by the gastric parietal cell. Gastric acid secretion plays an important role in the digestive process, and it is a major contributing factor in peptic ulcer disease and reflux esophagitis. Information on how gastric acid secretion is regulated, thus, would contribute both to gastrointestinal physiology and to the clinical management of gastrointestinal diseases. The specific aims of this proposal will seek to study the mechanisms which lead to activation of the gastric H-K ATPase, known to be responsible for proton transport by this tissue. One set of studies is designed to formulate a quantitative kinetic model for activation and inactivation of the proton pump in the intact parietal cell. These studies will employ the recently developed methods for measuring H-K ATPase activity in situ to estimate the number of active proton pumps in relation to acid secretory rate. Measurements of the number of active proton pumps under steady-state conditions and during the onset or recovery of secretion will be used to construct a quantitative model for active pump turnover. The results will be used to test the hypothesis that acid secretion is regulated by the distribution of H-K ATPase between active and inactive forms. A second set of studies will employ gastric membrane vesicles to characterize two transport processes, a Cl- conductance and a cation exchanger, which recently have been identified as existing in the same membrane as the H-K ATPase. These studies will provide information on the nature of these processes and their possible role in regulating the activity of the H-K ATPase. Additionally, since several projects employ omeprazole, a new antiulcer agent, information will be obtained on the mechanisms of action of this compound which could be important for understanding the clinical actions of this new therapeutic agent.