CGP 20712 A: a useful tool for quantitating beta 1- and beta 2-adrenoceptors

CGP 20712 A (1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3- [4-(1-methyl-4-trifluoromethyl-2-imidazolyl) phenoxy]-2-propanol methanesulfonate), a specific beta 1-adrenoceptor antagonist, was tested for resolution of beta 1- and beta 2-adrenoceptors in an in vitro [3H]dihydroalprenolol ([3H]DHA) binding assay. Competition experiments, using rat neocortical and cerebellar membranes, yielded two dissimilar concentration-effect curves. A distinct biphasic curve was evident for neocortex, with a plateau at 100 nM CGP 20712 A (60% [3H]DHA displacement). This plateau indicated a differentiation between beta 1- and beta 2-adrenoceptors; the ratio of IC50-beta 2 to IC50-beta 1 was approximately 10,000. In contrast, only a monophasic curve was obtained for cerebellum. CGP 20712 A is a useful tool for estimating percentages of beta 1- and beta 2-adrenoceptors in a given tissue.