NEURAL CONTROL OF BROWN FAT TRANSMEMBRANE SIGNALLING

棕色脂肪跨膜信号传导的神经控制

• 批准号: 3235649
• 负责人: James G Granneman
• 金额: $ 3.51万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3235649
• 关键词: G protein; adenylate cyclase; autoradiography; beta adrenergic receptor; biological signal transduction; brown fat; enzyme induction /repression; gel electrophoresis; laboratory rat; membrane proteins; messenger RNA; molecular cloning; neural information processing; neural transmission; neuroendocrine system; neurotransmitters; newborn animals; norepinephrine; perinatal; receptor expression; sympathetic nervous system; thermoreception; tissue /cell culture

Induction and maintenance of thermally active brown adipose tissue (BAT) depends to a large degree upon the activation of adenylate cyclase by the sympathetic nervous system. In contrast to many sympathetically-innervated tissues, physiologic levels of sympathetic stimulation produced by cold exposure increase, rather than decrease, the responsiveness of adenylate cyclase in BAT. Our work to date indicates that the neurally-mediated increase in catalytic activity is the result of an alteration of the stimulatory regulatory protein of adenylate cyclase (Gs). We have proposed a series of experiments to investigate fundamental issues raised by our observations. First, we will establish the nature of this alteration in Gs by combining immunochemical, electrophoretic and membrane fusion techniques. Second, we will investigate the impact of changes in Gs on its coupling to beta receptors and glucagon receptors. Finally, we seek to determine the anatomic distribution of glucagon and beta receptors in BAT, as well as determine the cell types that are subject to neural modulation. Induction and maintenance of thermally active BAT depends upon the interaction of neurotransmitters with specific transmembrane signalling systems. We propose to characterize these systems biochemically and anatomically, and examine how they are modified by chronic neural stimulation. In doing so, we hope to provide knowledge about the regulation of transmembrane signalling in general and, in particular, those systems in BAT, a tissue that has been implicated in the etiology of obesity.

热活性棕色脂肪的诱导和维持 组织（BAT）在很大程度上取决于 腺苷酸环化酶。 相比之下 对于许多交感神经支配的组织， 由冷暴露产生的交感神经刺激增加， 而不是降低，腺苷酸环化酶的反应性， 球棒 我们迄今为止的工作表明， 催化活性的增加是改变催化剂的性质的结果。 腺苷酸环化酶（Gs）刺激性调节蛋白。 我们提出了一系列的实验来研究 我们的观察所提出的基本问题。 一是 通过结合以下方式确定G中这种变化的性质： 免疫化学、电泳和膜融合 技术. 第二，我们将调查 Gs与β受体和胰高血糖素受体的偶联。 最后，我们试图确定的解剖分布， BAT中的胰高血糖素和β受体，以及决定细胞 受神经调节的类型。 热活性最佳可得技术的引入和维持取决于 神经递质与特异性跨膜 信号系统。 我们建议对这些系统进行表征 从生物化学和解剖学的角度， 被慢性神经刺激所改变 在这样做时，我们希望 提供跨膜调节的知识， 一般的信令系统，特别是最佳可得技术中的那些系统， 与肥胖症病因学有关的组织。