PERIPHERAL AND CENTRAL SATIETY ACTIONS OF BOMBESIN

描述（改编自申请人的摘要）： 本项目旨在了解内源性哺乳动物 蛙皮素样肽--胃泌素释放肽和神经介肽B (NMB)--在外周生成和中枢神经处理中， 生理信号，限制膳食的大小和调节的长度， 大鼠的餐间时间。 尽管越来越多的证据表明， GRP和NMB对动物和人类的两种功能都很重要， 关键的问题仍然没有解决：每一个行动的最初地点 肽，以及是否与正常膳食生理相关 格局 这些研究人员获得的结果表明， 施用的蛙皮素作用于上腹部，在床内， 腹腔动脉 他们认为内源性GRP和/或NMB最初起作用， 在胃里，对正常的胃功能做出重要的生理贡献。 膳食模式 为了建立正常的饮食模式，研究人员将聘请 自发进食，不受干扰的大鼠制备。 跟踪连续的 膳食和餐间间隔，并允许微观结构分析， 每顿饭，他们将记录下每秒钟的液体食物摄入量， 使用粘滞计。 为了确定行动地点，他们将提供玻璃钢， 通过闭合动脉输注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 对每种肽采用有效的高选择性受体拮抗剂。 这项研究将提供一个决定性的检验假设的风险： 从胃壁内神经释放的内源性GRP和NMB， 在当地采取行动，限制膳食量， 自发进食条件。 成功解决这一主要问题 将建立所需的基础，以了解特定的神经和 中枢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学位置。

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.