Neural and GI Substrates in Bombesin Satiety

铃蟾肽饱腹感的神经和胃肠道底物

• 批准号: 6543630
• 负责人: ELLEN E LADENHEIM
• 金额: $ 36.24万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6543630
• 关键词: appetite regulatory center; bioenergetics; biological signal transduction; body weight; bombesin; bombesin like peptide; gastrin releasing peptide; gene targeting; genetically modified animals; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; leptin; neural information processing; neurons; neuropeptide Y; neuropeptide receptor; nutrient intake activity; nutrition related tag; obesity; paraventricular nucleus; protein protein interaction; protein structure function; satiations; solitary tract nucleus

DESCRIPTION (provided by applicant): The overall goal of this proposal is to identify novel actions of mammalian bombesin (BN)-like peptides in the controls of food intake and energy balance. The mammalian BN-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been demonstrated to reduce food intake following both peripheral and central administration, but little is known about their underlying mechanisms of action. The proposed experiments examine aspects of three different hypotheses. The experiments under Specific Aim 1 will assess the idea that a GRP-ergic pathway from the hypothalamus to the caudal hindbrain plays a pivotal role in the ability of metabolic signals such as leptin to affect food intake through alterations in meal size. The experiments under Specific Aim 2 will focus on how metabolic signals indicating positive or negative energy balance alter the ability of peripheral and central GRP and NMB to inhibit food intake. Based on the demonstration that bombesin receptor subtype 3 (BRS-3) knockout mice are hyperphagic and obese, experiments under Specific Aim 3 will identify the role of this novel receptor signaling system in the control of food intake and energy balance. The experiments addressing these hypotheses will employ multiple measures of food intake and specific receptor agonists and antagonists to characterize intake and identify roles of specific receptor subpopulations, c-Fos expression as a measure of cellular activation to identify candidate brain sites where interactions occur and double-labeling techniques to characterize the phenotype of these cellular populations. Together, these studies will greatly enhance our understanding of the role of mammalian BN-like peptides in the interactions between short-term satiety signals and signals that regulate overall energy balance. Such an understanding will significantly enhance our understanding of the mechanisms underlying overall energy regulation and may lead to novel treatments for obesity or eating disorders

描述（由申请人提供）：该提案的总体目标是确定在食物摄入量和能量平衡控制中类似哺乳动物孟买（BN）的新作用。已证明哺乳动物BN样肽，胃蛋白释放肽（GRP）和神经蛋白B（NMB）可在外围和中央给药后降低食物摄入量，但对它们的基本作用机理知之甚少。提出的实验检查了三个不同假设的各个方面。在特定目标1下的实验将评估从下丘脑到尾骨后脑的GRP - 能途径在代谢信号（例如瘦素）通过饮食大小的改变来影响食物摄入的能力中起关键作用。特定目标2下的实验将集中于表明正能量平衡或负能量平衡的代谢信号如何改变外围和中央GRP和NMB抑制食物摄入的能力。基于孟买受体亚型3（BRS-3）敲除小鼠的证明是肥大和肥胖的，在特定目标3下的实验将确定这种新型受体信号系统在控制食物摄入和能量平衡中的作用。解决这些假设的实验将采用多种量度的食物摄入量和特定的受体激动剂和拮抗剂来表征摄入量并识别特定受体亚群的作用，C-FOS表达作为细胞激活的量度，以识别发生相互作用的候选脑站点，并表现出这些细胞群体现象的双重标记技术。总之，这些研究将大大增强我们对哺乳动物BN样肽在短期饱腹感和调节总体能量平衡的信号之间相互作用中的作用的理解。这种理解将显着增强我们对总体能量调节机制的理解，并可能导致肥胖或饮食失调的新治疗方法