GASTRIN'S TROPHIC EFFECT IN THE COLON

胃泌素在结肠中的营养作用

• 批准号: 3464518
• 负责人: RIHAB R YASSIN
• 金额: $ 10.97万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464518
• 关键词: autoradiography; biological signal transduction; calcium flux; cell cycle; cell growth regulation; colon; cyclic AMP; drug delivery systems; fluorescent dye /probe; gastrins; gel electrophoresis; guanine nucleotide binding protein; hormone receptor; hormone regulation /control mechanism; hydrolysis; inositol phosphates; intestinal mucosa; intracellular transport; laboratory rat; phosphatidylinositols; protein kinase C; protein sequence; tissue /cell culture

An increased understanding of the intracellular mechanisms regulating colonic epithelial cell proliferation is vital because it will provide an insight into the events associated with ulcer healing and malignant transformation. In this vein, numerous investigations have shown the hormone gastrin to be trophic to most of the mucosa of the digestive tract. However, the mechanisms by which gastrin stimulate mucosal growth have not been examined. We propose to identify the signals, the mechanisms that precede, and the intracellular events that regulate colonic epithelial trophic response to gastrin. Specifically. we will investigate whether gastrin stimulates polyphosphoinositide hydrolysis with subsequent Ca2+ mobilization, activates protein kinase C enzyme system, modulates the level of intracellular cAMP, and initiates its stimulatory effect by activating a guanine nucleotide binding protein. Corollary studies will also be carried out utilizing MC-26 gastrin responsive cell line and in vivo animal model. The ultimate hope is to unravel, in molecular terms, the pathways by which hormones regulate colonic epithelial cell proliferation. Pharmacological manipulation of these events may perhaps form the basis of a rationally designed selective therapeutic agents for ulcer healing and control of malignant transformation.

增加了对细胞内调节机制的理解， 结肠上皮细胞增殖是至关重要的，因为它将提供 深入了解与溃疡愈合和恶性肿瘤相关的事件 转型 在这方面，许多调查表明， 促胃液素对消化道粘膜有营养作用 道。 然而，胃泌素刺激粘膜生长的机制 还没有被检查过。 我们建议识别信号， 之前的机制，以及调节 结肠上皮对胃泌素的营养反应。 具体来说我们将 研究胃泌素是否刺激多磷酸肌醇水解 随后的Ca 2+动员，激活蛋白激酶C酶 系统，调节细胞内cAMP的水平，并启动其 通过激活鸟嘌呤核苷酸结合蛋白的刺激作用。 还将利用MC-26胃泌素进行推论研究 应答细胞系和体内动物模型。 最终的希望是 从分子角度解开激素调节的途径 结肠上皮细胞增殖。 药理学操作 这些事件也许可以形成一个合理设计的基础， 用于溃疡愈合和控制恶性肿瘤的选择性治疗剂 转型