ISOPROTERENOL AND SELECTIVE AGONISTS STIMULATE SIMILAR ATYPICAL BETA-ADRENOCEPTORS IN RAT ADIPOCYTES

We have demonstrated previously that (-)isoproterenol triggers lipolysis in rat epididymal fat cells by stimulating both classical (beta1, beta2) and atypical beta-adrenoceptors. The contribution of the classical beta-adrenoceptors can be blocked by addition of 3 nM CGP12177{di-4-3[(1,1-dimethylethyl)amino]-(2-hydroxylpropoxy)1,3-dihydro-2H-benzimidazol-2-one hydrochloride). At higher concentrations, CGP12177 triggers lipolysis also, but by stimulating atypical beta-adrenoceptors only. To find out whether (-)isoproterenol and CGP12177 stimulate similar atypical beta-adrenoceptors, we compared their interaction with recognised beta3-adrenoceptor antagonists: CGP20712 {1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-propan-2-ol} (beta1-selective), ICI118551 [erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamine)-butan-2-ol] (beta2-selective) and the stereoisomers as well as the racemic mixture of propanolol (non-beta1/beta2-subtype selective) and of metoprolol (beta1-selective). There was a highly significant relationship (r = 0.93) between the potencies of these antagonists for inhibiting the lipolytic response to (-)isoproterenol (in the absence of classical beta-adrenoceptor stimulation) and CGP12177. In both cases, propranolol and metoprolol showed also the same degree of stereoselectivity. These findings suggest that (-)isoproterenol and CGP12177 stimulate the same type and/or form of atypical beta-adrenoceptors in rat epididymal adipocytes.