NEURAL CONTROL OF BROWN FAT TRANSMEMBRANE SIGNALLING

热活性棕色脂肪的诱导和维持 组织(BAT)在很大程度上依赖于 交感神经系统的腺苷环化酶。相比之下， 对于许多交感神经支配的组织来说，生理水平 冷暴露产生的交感神经刺激增加， 腺苷环化酶的反应性非但没有降低，反而 蝙蝠。我们到目前为止的工作表明，神经调节的 催化剂活性的提高是由于改变了 腺苷环化酶刺激调节蛋白(Gs)。 我们已经提出了一系列实验来研究 我们的观察提出了一些基本问题。首先，我们将 通过组合来确定Gs中此更改的性质 免疫化学、电泳膜融合 技巧。第二，我们将调查以下变化的影响 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学分布 蝙蝠体内的胰高血糖素和β受体，以及决定细胞 受制于神经调节的类型。 热活性BAT的诱导和维持依赖于 神经递质与特异性跨膜的相互作用 信号系统。我们建议对这些系统进行刻画 生化和解剖学，并检查它们是如何 被慢性神经刺激所改变。通过这样做，我们希望 提供有关跨膜调节的知识 一般情况下，尤其是BAT中的那些系统， 与肥胖病因学有牵连的组织。

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.