PERIPHERAL AND CENTRAL SATIETY ACTIONS OF BOMBESIN

这个项目的长期目标是理解内源性的作用 哺乳动物蛙毒素样多肽在外周世代和 生理饱足感信号的中枢神经处理 限制进餐数量，并控制餐后中间餐的长度 在大鼠体内的间歇作用。 最近的结果表明：(1)饱腹感的作用部位 外周给药的蛙皮素位于上腹部， 可能在胃的内脏神经，(2)传入迷走神经和 脊髓-内脏神经集中传递蛙皮素引发的饱腹感信号， (3)后脑内源性蛙皮素样肽起关键作用。 在饱腹感信号的中央处理中，和(4)血清素 蛙皮素诱导的饱腹感的表达需要系统。 聚焦这四个问题，用最新发展的外科手术 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 胃内的蛙皮素样肽，以及内源性蛙皮素样肽 该部位的多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足感；(3) 在背侧后脑中的感受野对由 外周给药的蛙皮素样肽及其作用 该部位的内源性蛙皮素样多肽；以及(4)该基因座和 5-羟色胺受体亚型(S)介导蛙皮素样相互作用 饱腹感中的多肽系统和5-羟色胺系统。 如果蛙皮素家族的多肽被证明具有生理功能 外围和中心部位的餐后饱腹感的中介者，这 这一发现将对正常的分析产生根本的影响 摄食行为，并测定其病理生理和 治疗人类两种主要的饱腹症，神经性暴食症和 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.