In vivo desensitization of the beta, but not the alpha 2-adrenoreceptor-coupled-adenylate cyclase system in hamster white adipocytes after administration of epinephrine.
To assess the physiological relevance of the changes in adrenergic receptor observed in adipocyte membranes after in vitro exposure to catecholamines, hamster white adipocytes, which possess both beta- and alpha-adrenergic receptors, were studied after a 6-day in vivo epinephrine administration (1 mg/kg, daily). This treatment resulted in a 3-fold increase in total plasma catecholamine levels and in the following changes in the adipocytes. The lipolytic and cAMP responses to beta-agonists, ACTH, and theophylline were decreased by 55-60%, but the sensitivity of these responses to (-)isoproterenol was unchanged. Although basal adenylate cyclase activity was unaffected, (-)isoproterenol-, ACTH- or fluoride-stimulated activities were reduced by half, a defect which persisted in the presence of guanosine 5'-[beta, gamma-imido]triphosphate. Furthermore, the number of beta-adrenergic receptors was also decreased by 54%. In contrast, epinephrine treatment failed to impair the adipocyte antilipolytic response to the alpha 2-agonist clonidine, the alpha 2-component of epinephrine, and the adenosine analog N6-phenylisopropyladenosine, the adenylate cyclase inhibitory response to these compounds, and the number of alpha 2-adrenergic receptors. These results indicate that in vivo epinephrine administration does not alter the alpha 2-adrenergic system of hamster white adipocyte, but desensitizes the lipolytic response to beta-agonists and also to nonadrenergic lipolytic agents. It is therefore suggested that the likely mechanism(s) responsible for this lipolysis desensitization mainly consists in impaired adenylate cyclase coupling and possibly in altered intracellular processes, rather than in the observed beta-adrenergic receptor down-regulation.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D005990:Glycerol; D004837:Epinephrine