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

Abstract

The role of sinoatrial β₁- and β₂-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 β₁-adrenoceptors antagonist CGP 20712 A. The curves for (−)-adrenaline in the presence of 300 nmol/l CGP 20712 A (equivalent to 1,000 times its K _B, K _B=0.3 nmol/l for β₁-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 β₂-adrenoceptor-selective antagonist ICI 118,551. These results are consistent with an involvement in the rat of both β₁-adrenoceptors (to a major extent) and β₂-adrenoceptors [only at high (−)-adrenaline concentrations] in the positive chronotropic effects of (−)-adrenaline. (−)-Noradrenaline appears to activate mostly rat sinoatrial β₁-adrenoceptors.