Potentiation of in vivo thermogenesis in rat brown adipose tissue by stimulation of alpha 1-adrenoreceptors is associated with increased release of cyclic AMP.
Release of cyclic AMP (cAMP) from the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats given activators and inhibitors of brown adipose tissue (BAT) thermogenesis was assessed by measuring IBAT blood flow (microsphere method) and the arteriovenous difference in plasma cAMP across the tissue. The release was taken as an index of the generation of cAMP in the IBAT. During thermogenesis induced by infusion of graded doses of noradrenaline (NA), release of cAMP increased from no significant release without NA to 68 pmol/min at a NA dose that effected maximal thermogenesis. The alpha-adrenoreceptor antagonist dihydroergotoxin inhibited NA-induced BAT thermogenesis and markedly reduced the release of cAMP. The alpha 1-adrenoreceptor agonist phenylephrine potentiated the in vivo thermogenic response of BAT to isoproterenol or to a suboptimal dose of NA and enhanced the release of cAMP elicited by these catecholamines. But given alone, phenylephrine or dihydroergotoxin had very little or no effect on thermogenesis and cAMP release. These results suggest that stimulation of the alpha 1-adrenoreceptors on BAT adipocytes potentiates the thermogenic response originating from stimulation of the adenylate cyclase-coupled beta 1-adrenoreceptors by increasing, in some indirect way, the generation of cAMP, the intracellular messenger for activation of thermogenesis. However, in the absence of proof that adipocytes are the principal source of the cAMP released from IBAT, during catecholamine-induced thermogenesis, this explanation for the effect of alpha 1-adrenoreceptor stimulation on thermogenesis remains tentative.
D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D004088:Dihydroergotoxine / Q000494:pharmacology; D006400:Hematocrit; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow
D000316:Adrenergic alpha-Agonists; D004088:Dihydroergotoxine; D010656:Phenylephrine; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine