The beta 1-adrenoceptor antagonist CGP 20712 A unmasks beta 2-adrenoceptors activated by (-)-adrenaline in rat sinoatrial node.

Abstract

The role of sinoatrial beta 1- and beta 2-adrenoceptors mediating positive chronotropic effects of (-)-adrenaline and (-)-noradrenaline was investigated in rat right atria. Concentration effect curves for (-)-adrenaline, but not for (-)-noradrenaline, became biphasic in the presence of the beta 1-adrenoceptor antagonist CGP 20712 A. The curves for (-)-adrenaline in the presence of 300 nmol/l CGP 20712 A (equivalent to 1,000 times its KB, KB = 0.3 nmol/l for beta 1-adrenoceptors) comprise a high-sensitivity component that saturates at 1/4 of maximum effect, and a low sensitivity component. The high-sensitivity component is blocked by the beta 2-adrenoceptor-selective antagonist ICI 118,551. These results are consistent with an involvement in the rat of both beta 1-adrenoceptors (to a major extent) and beta 2-adrenoceptors [only at high (-)-adrenaline concentrations] in the positive chronotropic effects of (-)-adrenaline. (-)-Noradrenaline appears to activate mostly rat sinoatrial beta 1-adrenoceptors.