NEURAL SUBSTRATES OF PEPTIDE-INDUCED SATIETY

描述(改编自申请人的摘要)：长期目标 这项工作的一部分是识别神经系统，通过这些多肽 影响食物摄入量，以从解剖学和生物学角度描述这些系统 在功能上，并最终理解多肽和神经元是如何 调解他们的行为，参与生理和/或 病理引起的食物摄入量的变化。 首席调查员(PI)一直专注于 缩胆囊素(CCK)对食物摄入量的调节作用 在肠道和脑中发现。他发现，CCK通过 当一些营养素被放置在食物中时，食物摄入量的减少 小肠。拟议中的实验旨在确定 调节食物摄入量减少的CCK作用以及在什么类型 它作用于感受器。为了实现这些目的，这些实验解决了 以下三个具体目的：1)使用药理学和免疫学 方法结合限制用药鉴定一般情况。 参与抑制假手术的CCK受体的定位和亚型 通过肠道营养进行喂养；2)利用肠道内输注 使肠道神经元脱敏的药物以评估局部 肠道抑制摄食中的肠神经支配 营养素和外源性CCK；以及3)使用免疫组织化学技术 从解剖学上识别中枢和外周神经元由 肠道刺激和外源性多肽。

DESCRIPTION (ADAPTED FROM THE APPLICANT'S ABSTRACT): The long term goals of this work are to identify the neuronal systems through which peptides influence food intake, to characterize these systems both anatomically and functionally, and ultimately to appreciate how peptides and the neurons that mediate their actions participate in physiologically and/or pathologically-induced changes in food intake. The Principal Investigator (PI) has concentrated on neural systems that mediate suppression of food intake by cholecystokinin (CCK), a peptide found in the intestine and in the brain. He has found that CCK mediates reductions of food intake that occur when some nutrients are placed in the small intestine. The proposed experiments are designed to determine where the CCK that mediates reduction of food intake acts and at what type of receptors it acts. To accomplish these ends the experiments address the three following specific aims: 1) use pharmacological and immunological methods together with restricted drug application to identify the general location and subtype of the CCK receptors involved in suppression of sham feeding by intestinal nutrients; 2) utilize intraintestinal infusions of agents that desensitize gut neurons to assess the role of the local intestinal innervation in suppression of food intake by intestinal nutrients and exogenous CCK; and 3) use immuno-histochemical techniques to anatomically identify central and peripheral neurons that are activated by intestinal stimuli and exogenous peptides.