ANALYSIS OF THE SATIETY EFFECT OF CHOLECYSTOKININ

缩胆囊素的饱腹感作用分析

• 批准号: 3377866
• 负责人: GERARD P SMITH
• 金额: $ 14.96万
• 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 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3377866
• 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.

摄入的食物终止进食的生理机制 动物和人类未知。 关于此类机制的知识是 开发有效的治疗方法来控制 在临床状况下进食，例如肥胖和贪食症。 这个提议 检验以下假设：小肠肽激素称为 胆囊收缩素（CCK）是由接触食物刺激物释放的 小肠表面是其生理机制之一 结束一顿饭并引发餐后特征的行为 大鼠的饱腹感。 将使用放射免疫分析技术来测量 通过十二指肠内注射脂肪混合物或通过 L-苯丙氨酸。 CCK的释放方式及数量为 与假喂养产生的抑制作用相关 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、Proglumide 和 胃迷走神经切断术，对十二指肠输注的饱足效果 释放CCK。 如果释放的 CCK 显示抑制假喂养，则 释放的 CCK 对真正进餐终止的饱足效果将 可以使用拮抗策略来确定。 除了测试 假设肠道释放的CCK是一种生理饱足感 信号，建议进行实验以确定 CCK 的外围位点 饱腹感效果。 CCK 的特定绑定程序将用于 确定完全和选择性胃迷走神经切断术对 CCK 的影响 幽门括约肌中的结合位点。 这将决定是否 结合位点位于迷走神经的末端纤维或其他部位 括约肌中的元件，即括约肌的肌肉细胞或内在神经元 肠道。 最终实验将确定束核中的位置 髓质中的孤独肌是迷走神经传导所必需的 外周给予外源性CCK或产生的传入活性 将内源性 CCK 释放为中央使用的信息 用于控制进食以停止进食并启动餐后的网络 饱腹感。