PERIPHERAL AND CENTRAL SATIETY ACTIONS OF BOMBESIN

本项目的长期目标是了解内源性 哺乳动物蛙皮素样肽在外周代和 生理饱足感信号的中枢神经处理， 限制进餐量和调节餐后间隔时间 在大鼠中间隔。 最近的研究结果表明：（1） 外周给药蛙皮素位于上腹部， 可能在胃的内在神经，（2）传入迷走神经， 脊-内脏神经中枢地传递铃蟾肽引发的饱足感信号， (3)后脑内源性蛙皮素样肽在 在饱腹感信号的中央处理中，以及（4）血清素 系统是蛙皮素诱导的饱腹感的表达所必需的。 针对这四个问题，采用新开发的外科 技术，化学消融和选择性拮抗剂，我们将 确定：（1）外周给药的具体作用部位 胃内是否存在内源性蛙皮素样肽， 该位点的肽是正常饱腹感所必需的;（2）特定的 脊髓-内脏通路介导蛙皮素诱导的饱腹感;（3） 背侧后脑对饱腹感信号的感受野 外周给药的蛙皮素样肽，以及 在该位点的内源性铃蟾肽样肽;和（4）该基因座和 5-羟色胺受体亚型介导蛙皮素样 肽系统和血清素系统在饱腹感中的作用。 如果蛙皮素家族的肽被证明是作为一种生理功能， 在外周和中枢部位的餐后饱腹感的调节剂， 这一发现将对分析正常的 摄食行为和用于确定病理生理学， 治疗人类两种主要的饱腹感障碍，神经性贪食症和 肥胖

The long-term goal of this project is to understand the roles of endogenous mammalian bombesin-like peptides in the peripheral generation and in the central neural processing of the physiological satiety signals which serve to limit meal size and to regulate the length of the postprandial intermeal interval in rats. Recent results indicate (1) that the site of the satiety action of peripherally-administered bombesin is located in the upper abdomen, probably in intrinsic nerves of the stomach, (2) that afferent vagal and spinal-visceral nerves relay bombesin-initiated satiety signals centrally, (3) that endogenous bombesin-like peptides of the hindbrain play a key role in the central processing of satiety signals, and (4) that serotonin systems are required for the expression of bombesin-induced satiety. Focussing on these four issues, and using newly-developed surgical techniques, chemical ablations, and selective antagonists, we will determine: (1) the specific site of action of peripherally-administered bombesin-like peptides within stomach, and whether endogenous bombesin-like peptides at that site are necessary for normal satiety; (2) the specific spinal-visceral pathways mediating bombesin-induced satiety; (3) the receptive field in dorsal hindbrain for satiety signals generated by peripherally-administered bombesin-like peptides, and the role of endogenous bombesin-like peptides at that site; and (4) the locus and serotonin receptor subtype(s) mediating interactions between bombesin-like peptide systems and serotonin systems in satiety. If the bombesin family of peptides is shown to function as a physiological mediator of postprandial satiety at peripheral and central sites, this finding will have fundamental implications for the analysis of normal feeding behavior and for the determination of the pathophysiology and treatment of the two major satiety disorders in humans, bulimia nervosa and obesity.