INTRACELLULAR REACTIONS IN GASTRIC MUCOSA

该项目的长期目标是确定和表征 盐酸分泌的细胞内反应 被胃壁细胞吞噬胃酸分泌在 在消化过程中的作用，它是一个主要的贡献因素， 消化性溃疡和反流性食管炎。信息如何胃 酸分泌受到调节，因此，将有助于 胃肠道生理学和临床管理 胃肠道疾病 本提案的具体目标是研究 导致胃H-K ATP酶的激活，已知该酶负责 质子的运输。其中一组研究旨在 制定了一个定量动力学模型的激活和失活， 完整的壁细胞中的质子泵这些研究将采用 最近开发的原位测量H-K ATP酶活性的方法， 估计与酸分泌有关的活跃质子泵的数量 率稳态质子泵激活数的测量 条件下和在分泌开始或恢复期间，将用于 建立主动泵周转的定量模型。结果将 可用于检验酸分泌受以下因素调节的假设： H-K ATP酶在活性和非活性形式之间的分布。第二组 的研究将采用胃膜囊泡来表征两种 运输过程，Cl-电导和阳离子交换剂， 最近已被确定为存在于相同的膜作为H-K ATP酶这些研究将提供关于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 ATP酶此外，由于几个项目采用奥美拉唑， 抗溃疡剂，将获得有关作用机制的信息 这种化合物对于理解临床上 这种新的治疗药物的作用。

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.