ANALYSIS OF THE SATIETY EFFECT OF CHOLECYSTOKININ

摄取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 对于开发有效的防治方法是必要的 在临床条件下进食，如肥胖和暴食症。这项建议 测试了一种假设，即小肠肽荷尔蒙称为 胆囊素(CCK)是由食物刺激接触 小肠表面是致病的生理机制之一。 结束一顿饭并引出餐后行为的特点 老鼠的饱腹感。将使用放射免疫分析技术来测量 十二指肠内注入混合脂肪或经十二指肠注射释放CCK L-苯丙氨酸。CCK发布的模式和数量将是 与抑制假喂食有关，由 十二指肠内输液。这种关联的因果性质将是 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灌流充盈作用的影响 释放CCK。如果释放的CCK被显示为抑制假喂食，那么 释放的CCK对终止一顿真正的饭的饱腹感将 使用对抗性策略来确定。除了测试 假设从肠道释放的CCK是一种生理饱足感 信号，建议用实验来确定CCK的外围位置 饱腹感。CCK的特定绑定程序将用于 全胃迷走神经切断术和选择性胃迷走神经切断术对CCK的影响 幽门括约肌的结合部位。这将决定是否 结合部位位于迷走神经的终末纤维或其他 括约肌中的成分，即肌肉细胞或 直觉。最后的实验将确定这个部位在束核中。 迷走神经转导所必需的延髓孤立性 外周注射外源性CCK或 将内源性CCK释放为中央使用的信息 控制进食停止进食和开始餐后进食的网络 饱腹感。

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.