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INTRACELLULAR REACTIONS IN GASTRIC MUCOSA

胃粘膜的细胞内反应

基本信息

批准号：
3150931
负责人：
STEPHEN J HERSEY
金额：
$ 15.25万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-12-01 至 1989-11-30
项目状态：
已结题

项目摘要

The longterm goal of this program is to describe the sequence of cellular reactions which lead to the secretion of hydrochloric acid by the gastric mucosa with emphasis on those reactions which serve as the major controlling steps. Recent interest in this area derives from the success of antisecretory agents in the clinical management of ulcer disease and the appreciation of the important role of proton transport in various biological processes. The current proposal seeks to extend previous observations concerning the cellular control of acid secretion so as to provide a more detailed understanding of the control mechanisms. Projects will utilize the recently developed preparations of isolated gastric glands and digitonin-permeabilized cells as well as the more traditional amphibian gastric mucosa as in vitro models. A combination of modern biophysical, biochemical, and morphological techniques will be used to investigate selected aspects of cellular control mechanisms. The major areas to be investigated include: 1) regulation of histamine H2-receptor; 2) the role of protein kinases, specifically the cAMP-dependent and calcium/phospholipid-dependent enzymes; 3) the basic mechanisms involved in the morphological transition of the parietal cell which occurs with stimulation; 4) the relationship between mitochondrial metabolism and proton transport; and 5) the effects of omeprazole, an H-KATPase inhibitor, on ion transport mechanisms. These areas are identified as important regulatory sites, the investigation of which are timely and promises a high rate of progress towards the longterm goal.

该计划的长期目标是描述细胞序列导致胃酸分泌的反应粘膜，重点是那些反应，作为主要的控制步骤。最近对这一领域的兴趣源于其成功抗分泌剂在溃疡病临床治疗中的应用认识到质子运输在各种生物过程。目前的建议旨在扩大以前关于细胞控制酸分泌，以便提供更详细的了解控制机制。项目将利用最近开发的离体胃腺制剂，毛地黄皂苷透化细胞以及更传统的两栖动物胃粘膜作为体外模型。结合现代生物物理学，生物化学和形态学技术将用于研究蜂窝控制机制的选定方面。主要领域是研究内容包括：1）组胺H2-受体的调节; 2）组胺H2-受体的作用蛋白激酶，特别是cAMP依赖性和钙/磷脂依赖酶; 3）参与的基本机制壁细胞的形态转变，刺激; 4）线粒体代谢与质子转运;和5）奥美拉唑，一种H-KATP酶抑制剂，离子传输机制这些领域被确定为重要的监管场所，调查及时，承诺高实现长期目标的进度。