INTRACELLULAR REACTIONS IN GASTRIC MUCOSA

这个计划的长期目标是描述细胞的序列， 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来自于 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。

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.