NEURAL AND GI SUBSTRATES IN BOMBESIN SATIETY

蟾蜍素饱足感的神经和胃肠道底物

• 批准号: 2145674
• 负责人: ELLEN E LADENHEIM
• 金额: $ 18.02万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145674
• 关键词: appetite; appetite regulatory center; autoradiography; bombesin; gastrointestinal function; laboratory rat; neuropeptide receptor; neuropeptides; nutrient intake activity; nutrition related tag; protein structure; receptor binding; solitary tract nucleus

The overall aim of the research proposed in this grant is to identify the sites of action and mechanisms through which centrally and peripherally administered bombesin-like peptides affect food intake. Underlying these experiments is the view that bombesin (BBS) interacts with a variety of receptor populations in mammals, mimicking the effects of mammalian peptides such as gastrin releasing peptide (GRP) and neuromedin B (NMB) and that the inhibition of food intake is a physiological action of one or more of these endogenous mammalian peptides. The specific experiments take a number of directions. Utilizing receptor binding techniques and in vitro autoradiography, we propose to identify subpopulations of BBS binding sites for the mammalian peptides GRP and NMB, differentiated by their pharmacological specificity. We will determine the distribution and relative specificity of these BBS receptor subtypes in specific brain regions, the gastrointestinal tract and the spinal cord. We will use general and specific BBS receptor antagonists to identify the role of endogenous BBS-like peptides in the control of food intake and which actions of BBS are likely mediated by different specific receptor subpopulations. We will also use BBS agonist compounds with high degrees of specificity for one or the other receptor subtypes to identify local gastrointestinal actions of BBS-like peptides that may play a role in their ability to inhibit food intake. BBS agonists and antagonists will also be used to identify the mammalian peptides whose behavioral actions exogenous BBS is mimicking. Finally, we will identify the specific anatomical location of BBS receptors in the nucleus tractus solitarius (NTS) and determine the role of these receptors in the inhibition of food intake elicited by either centrally or peripherally administered BBS. Elucidation of this role will enable us to identify the relationship between the inhibition of food intake produced by both routes of administration. This work will also identify brain sites at which other behavioral actions of centrally administered BBS are mediated and the specific receptor subpopulations which may underlie these behavioral actions. Together, these experiments will significantly advance our understanding of the feeding inhibitory actions of BBS-like peptides specifically and brain/gut peptides in general. Our results will also provide a framework for understanding the overall functions of BBS-like peptides in behavior and neuro and gastrointestinal physiology.

该赠款提出的研究的总体目的是确定 动作和机制的集中和周边 施用的类似孟买的肽会影响食物摄入。 这些基础 实验是孟买（BBS）与多种相互作用的观点 哺乳动物中的受体种群，模仿哺乳动物的作用 肽等肽释放肽（GRP）和神经蛋白B（NMB） 并且对食物摄入的抑制是一个或 这些内源性哺乳动物肽中的更多。 具体实验 采取多个指示。 利用受体结合技术和 体外自显影术，我们建议确定BBS的亚群 哺乳动物肽GRP和NMB的结合位点，由 它们的药理特异性。 我们将确定分布和 这些BBS受体亚型在特定大脑中的相对特异性 区域，胃肠道和脊髓。 我们将使用 一般和特定的BBS受体拮抗剂，以确定 内源性BBS样肽在控制食物摄入量中 BB的作用可能是由不同特定受体介导的 亚群。我们还将使用高度的BBS激动剂化合物 一种或另一种受体亚型的特异性以识别局部 BBS样肽的胃肠道动作可能在 他们抑制食物摄入量的能力。 BBS激动剂和反对者将 还可以用来识别其行为作用的哺乳动物肽 外源性BB正在模仿。最后，我们将确定具体 BBS受体在细胞核solitarius中的解剖位置 （NTS）并确定这些受体在抑制食物中的作用 由中央或外围给药的BBS引起的摄入量。 阐明这一角色将使我们能够确定关系 在两种路线产生的食物摄入的抑制之间 行政。 这项工作还将确定其他其他部位 中央施用BB的行为行为是介导的，并且 可能是这些行为的特定受体亚群 动作。这些实验将大大推动我们的 了解BBS样肽的喂养抑制作用 通常，通常是大脑/肠肽。 我们的结果也将 提供一个框架来理解类似BBS的整体功能 行为，神经和胃肠道生理学的肽。