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.
McPherson
G A
GA
Molenaar
P
P
Malta
E
E
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014590:Uterine Contraction / Q000187:drug effects
D002395:Catecholamines; D009125:Muscle Relaxants, Central; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine