GASTRINS TROPHIC EFFECT IN THE COLON

胃泌素在结肠中的营养作用

• 批准号: 2143599
• 负责人: RIHAB R YASSIN
• 金额: $ 11.81万
• 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 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2143599
• 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

项目成果

Early signalling mechanism in colonic epithelial cell response to gastrin.

结肠上皮细胞对胃泌素反应的早期信号机制。

• DOI: 10.1042/bj3110945
• 发表时间: 1995
• 期刊: The Biochemical journal
• 作者: Yassin,RR;Little,KM
• 通讯作者: Little,KM

Gastrin's trophic effect in the colon: identification of a signaling pathway mediated by protein kinase C.

胃泌素在结肠中的营养作用：蛋白激酶 C 介导的信号通路的鉴定。

• DOI: 10.1016/0196-9781(93)90164-c
• 发表时间: 1993
• 期刊: Peptides
• 影响因子: 3
• 作者: Yassin,RR;Clearfield,HR;Little,KM
• 通讯作者: Little,KM