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.
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