GASTRIN'S TROPHIC EFFECT IN THE COLON

加深对细胞内调节机制的理解 结肠上皮细胞的增殖至关重要，因为它将为 洞察与溃疡愈合和恶性相关的事件 转型。在这方面，大量调查表明， 激素胃泌素对消化系统的大部分粘膜有营养作用 一条小路。然而，胃泌素刺激粘膜生长的机制 都没有经过检查。我们建议识别信号、 之前的机制，以及调节细胞内事件 结肠上皮对胃泌素的营养反应。具体地说。我们会的 胃泌素是否刺激多磷肌醇水解物的研究 在随后的钙离子动员中，激活蛋白激酶C酶 系统，调节细胞内cAMP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。 使用MC-26胃泌素也将进行相应的研究 响应性细胞系和体内动物模型。最终的希望是 从分子角度解开荷尔蒙调节的途径 结肠上皮细胞增殖。药理手法 这些事件可能构成了理性设计的基础 溃疡愈合和恶性疾病控制的选择性治疗药物 转型。

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.