Adrenergic Receptors Regulating cAMP Generation and Thermogenesis in Isolated Brown Adipocytes

Sammanfattning: Adrenoceptors are the functional receptors in brown adipocytes. In the present study, the second messenger cAMP - and thermogenesis (which is an index of the energy metabolism of brown adipocytes) - were measured in order to reveal the intricate mechanism of effects generated by various adrenoceptor interactions with agonists and antagonists on brown adipocytes from hamster, mouse and rat. A modified and advanced preparative method for the isolation of brown adipocytes from mouse and rat was established in order to provide cells for carrying out this investigation. Brown adipocytes from 4oC-acclimated rats were successfully and directly isolated by this method.b3-Adrenoceptors are the predominant if not exclusive receptors mediating thermogenesis in hamster, rat and mouse brown adipocytes.Arotinolol and carteolol behaved as b3-adrenoceptor agonists with low and partial activity. They will perhaps be useful chemical probes for defining adrenoceptor subtypes, recognising the molecular characteristics of the adrenoceptor protein and may be for curing obesity and diabetes.Glucagon acutely stimulates thermogenesis in isolated brown adipocytes, but does not seem to be able to stimulate thermogenesis in vivo. The Ca2+-antagonist benidipine stimulates thermogenesis only indirectly, through activation of the sympathetic nervous systerm.a1-Adrenoceptors are in themselves unable to increase cAMP accumulation and thermogenesis, but potentiate the thermogenic effect of the b3-adrenoceptor-elicited cAMP accumulation. Only at limiting and ''physiological'' cAMP levels, do the a1-adrenoceptors demonstrate this quantitatively significant effect on b3-adrenoceptor-mediated thermogenesis. The evidence suggests that a1 / b3 and Ca2+/cAMP synergism exists in the regulation of acute thermogenesis, and this may be the normal physiological mechanism.