ANALYSIS OF THE SATIETY EFFECT OF CHOLECYSTOKININ

缩胆囊素的饱腹感作用分析

• 批准号: 3377862
• 负责人: GERARD P SMITH
• 金额: $ 9.26万
• 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 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3377862
• 关键词: anorexic agent; anticholinergic agent; cholecystokinin; dietary lipid; eating; gastrointestinal nutrient absorption; hormone regulation /control mechanism; nutrition related tag; phenylalanine; pyloric region; radioimmunoassay; satiations; vagotomy

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.

摄入的食物终止进食的生理机制 动物和人类是未知的。 关于这种机制的知识是 开发有效的治疗方法以控制 在临床条件下进食，如肥胖和贪食症。 这项建议 测试了一个假设，即小肠肽激素称为 胆囊收缩素（CCK）是由食物刺激释放接触 小肠表面是一种生理机制， 结束一顿饭，并引发餐后行为特征， 老鼠的饱腹感 放射免疫分析技术将用于测量 通过十二指肠内输注脂肪混合物或通过 L-苯丙氨酸 CCK释放的模式和数量将 与抑制假喂养产生的 十二指肠内输注。 这种相关性的因果性质将是 通过测量CCK拮抗剂丙谷胺和 胃迷走神经切断术，对十二指肠输注的饱足作用， 释放CCK。 如果释放的CCK显示出抑制假喂食，那么 释放的CCK对结束真实的进餐的饱足作用将 使用拮抗剂策略确定。 除了测试 假设从肠道释放的CCK是一种生理饱腹感 信号，实验提出了确定CCK的周边网站 饱腹效应 将使用CCK的特定结合程序来 确定完全和选择性胃迷走神经切断术对CCK的影响 幽门括约肌的结合位点 这将决定 结合位点在迷走神经的末端纤维上或在其它神经纤维上。 括约肌中的元件，即，肌肉细胞或内在神经元的 直觉 最后的实验将确定在束核的网站 延髓中的孤束流是迷走神经传导所必需的 外周给予外源性CCK或 内源性CCK释放成中枢神经系统所使用的信息， 用于控制进食以停止进食并启动餐后饮食的网络 饱腹感