CORRELATION OF BETA-3-ADRENOCEPTOR-INDUCED ACTIVATION OF CYCLIC-AMP-DEPENDENT PROTEIN-KINASE WITH ACTIVATION OF LIPOLYSIS IN RAT WHITE ADIPOCYTES

The lipolytic action of the beta3-adrenoceptor-selective agonist (3-ch lorophenyl)ethyl)-amino]propyl]-phenoxyacetic acid(BRL37344) was compa red to that of isoprenaline in adipocytes derived from rat white adipo se tissue. Concentration-response curves for activation of lipolysis b y each agonist correlated well with the dose-response curves for activ ation of cAMP-dependent protein kinase (A-Kinase). Addition of propran olol at a concentration (0.1 muM) sufficient to block beta1- and beta2 -adrenoceptors did not affect the stimulation of either parameter by B RL 37344 or isoprenaline, indicating that lipolysis was predominantly dependent on beta3-adrenoceptor stimulation. Blockade of beta3-adrenoc eptors by 3 muM propranolol antagonized both A-Kinase activation and g lycerol release. Activation of lipolysis by BRL 37344 was blocked by t reatment of the cells with omocinnamylamino)ethyl]-5-isoquinolinesulph onamide (H89) a potent and selective isoquinolinesulphonamide inhibito r of A-Kinase activity. Taken together, these results indicate that li polysis in rat white adipocytes is primarily controlled by beta3-adren oceptors, and that cyclic AMP generation alone is responsible for acti vation of lipolysis in this tissue.