PERIPHERAL AND CENTRAL SATIETY ACTIONS OF BOMBESIN

描述(改编自申请者摘要)：远景目标 这个项目是为了了解内源性哺乳动物的作用。 蛙皮素样肽--胃泌素释放肽(GRP)和神经梅毒素B (NMB)--在外周产生和中枢神经处理中 限制进餐数量和调节食物长度的生理信号 大鼠进食间隔时间。尽管有越来越多的证据表明内生性 GRP和NMB对动物和人类的两种功能都很重要， 关键问题仍未解决：每个问题的初始行动地点 多肽，以及两者是否在生理上与正常膳食相关 图案。 这些调查人员获得的结果表明，在外围 给药蛙皮素作用于上腹部，在床上 腹主动脉。他们认为内源性GRP和/或NMB最初起作用 在胃里，做出了重要的生理贡献 进餐模式。 为了建立正常的饮食模式，调查人员将雇用一名 自发喂食，原封不动的大鼠制剂。跟踪序列的步骤 餐食和餐间间隔，并允许进行微观结构分析 每餐一餐，他们将记录一秒又一秒的液体食物摄入量 用舔舌计。为了定位行动地点，他们将提供GRP和 近距离动脉输注NMB至上部器官选择性部位 腹部。为了确定GRP和NMB的生理相关性，他们将 为每种多肽使用有效的、高选择性的受体拮抗剂。 这项研究将对风险假设进行决定性的检验： 胃壁内神经释放的内源性GRP和NMB， 在以下情况下，在当地采取行动，限制用餐数量和调整用餐间隔时间 自然摄食条件。成功解决这一主要问题 将建立所需的基础来理解特定的神经和 集中传递这些肽引发的饱腹感信号的体液事件， 以及它们进入脑组织的解剖位置。

DESCRIPTION (adapted from applicant's abstract): The long-range goal of this project is to understand the roles of endogenous mammalian bombesin-like peptides -- gastrin releasing peptide (GRP) and neuromedin B (NMB) -- in the peripheral generation and central neural processing of the physiological signals that limit meal size and regulate the length of the intermeal interval in rats. Despite accumulating evidence that endogenous GRP and NMB are important for both functions in animals and humans, two critical problems remain unsolved: the initial site of action for each peptide, and whether either is physiologically relevant to the normal meal pattern. Results obtained by these investigators demonstrate that peripherally administered bombesin acts in the upper abdomen, within the bed of the coeliac artery. They propose that endogenous GRP and/or NMB act initially in the stomach, making an important physiological contribution to the normal meal pattern. To establish a normal meal pattern, the investigators will employ a spontaneously feeding, undisturbed rat preparation. To track sequential meals and intermeal intervals, and to permit the microstructural analysis of individual meals, they will record second-by-second intakes of liquid food using lickometers. To locate the sites of action, they will deliver GRP and NMB by close arterial infusion to organ-selective sites in the upper abdomen. To determine the physiological relevance of GRP and NMB, they will employ potent, highly-selective receptor antagonists for each peptide. This research will provide a decisive test of the hypothesis at risk: Endogenous GRP and NMB, released from intrinsic nerves in the stomach wall, act locally to limit meal size and regulate intermeal interval length under spontaneous feeding conditions. Successful resolution of this primary issue will establish the base required to understand the specific neural and humoral events that relay these peptide-initiated satiety signals centrally, and their anatomical sites of entry into brain tissue.