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 4-[2-[(2-hydroxy-2-(3-chlorophenyl)ethyl)-amino]propyl]-phenoxyacetic acid(BRL37344) was compared to that of isoprenaline in adipocytes derived from rat white adipose tissue. Concentration-response curves for activation of lipolysis by each agonist correlated well with the dose-response curves for activation of cAMP-dependent protein kinase (A-Kinase). Addition of propranolol at a concentration (0.1 muM) sufficient to block beta1- and beta2-adrenoceptors did not affect the stimulation of either parameter by BRL 37344 or isoprenaline, indicating that lipolysis was predominantly dependent on beta3-adrenoceptor stimulation. Blockade of beta3-adrenoceptors by 3 muM propranolol antagonized both A-Kinase activation and glycerol release. Activation of lipolysis by BRL 37344 was blocked by treatment of the cells with N-[2-p-(bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H89) a potent and selective isoquinolinesulphonamide inhibitor of A-Kinase activity. Taken together, these results indicate that lipolysis in rat white adipocytes is primarily controlled by beta3-adrenoceptors, and that cyclic AMP generation alone is responsible for activation of lipolysis in this tissue.