ANALYSIS OF THE SATIETY EFFECT OF CHOLECYSTOKININ

缩胆囊素的饱腹感作用分析

• 批准号: 3377864
• 负责人: GERARD P SMITH
• 金额: $ 13.84万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3377864
• 关键词: anorexic agent; anticholinergic agent; cholecystokinin; dietary lipid; eating; gastrointestinal nutrient absorption; hormone regulation /control mechanism; laboratory rat; nutrition related tag; phenylalanine; pyloric region; radioimmunoassay; satiations; vagotomy; vagus nerve

The physiological mechanisms by which ingested food terminates eating in animals and humans is unknown. Knowledge about such mechanisms is necessary for the development of effective treatments for the control of eating in clinical conditions, such as obesity and bulimia. This proposal tests the hypothesis that the small intestinal peptide hormone called cholecystokinin (CCK) that is released by food stimuli contacting the surface of the small intestine is one of the physiological mechanisms for ending a meal and eliciting the behaviors characteristic of postprandial satiety in the rat. A radioimmunoassay technique will be used to measure the release of CCK by the intraduodenal infusion of a mixture of fats or by L-phenylalanine. The pattern and quantity of CCK released will be correlated with the inhibition of sham feeding produced by the intraduodenal infusions. The causal nature of this correlation will be investigated by measuring the effect of CCK antagonists, Proglumide and gastric vagotomy, on the satiating effect of the duodenal infusions that release CCK. If the released CCK is shown to inhibit sham feeding, then the satiating effect of released CCK on the termination of a real meal will be determined using the antagonist strategy. In addition to testing the hypothesis that CCK released from the intestine is a physiological satiety signal, experiments are proposed to determine the peripheral site of CCK's satiety effect. A specific binding procedure for CCK will be used to determine the effect of total and selective gastric vagotomy on the CCK binding sites in the pyloric sphincter. This will decide whether the binding sites are on terminal fibers of the vagus nerve or on other elements in the sphincter, i.e., muscle cells or intrinsic neurons of the gut. The final experiment will identify the site in the nucleus tractus solitarius in the medulla that is necessary for the transduction of vagal afferent activity produced by peripheral administration of exogenous CCK or the release of endogenous CCK into information that is used by the central network for the control of feeding to stop eating and initiate postprandial satiety.

停止进食：摄入的食物停止进食的生理机制