The affinity and efficacy of naturally occurring catecholamines at beta-adrenoceptor subtypes.

The contribution of affinity and efficacy to the agonistic actions of the naturally occurring catecholamines, (-)-noradrenaline and (-)-adrenaline at beta-adrenoceptor sites were assessed in guinea-pig driven left atrial (beta 1) and K+-depolarized uterine (beta 2) preparations. The dissociation constants of each agonist, required in these calculations, were calculated using radioligand binding techniques. [125I]Iodocyanopindolol bound to sites in membrane preparations of each tissue which have been shown to represent beta 1-(atria) and beta 2-(uterus) adrenoceptors. It was found that (-)-noradrenaline was approximately 10-fold more selective for the beta 1- as opposed to the beta 2-adrenoceptor in the pharmacological studies. Affinity/efficacy calculations indicated that this selectivity was entirely due to a selective affinity for the beta 1-adrenoceptor subtype. (-)-Noradrenaline, (-)-adrenaline and the reference compound (-)-isoprenaline all had approximately the same efficacy at either beta-adrenoceptor subtype.