(+/-)-3HEpinephrine and (-)3Hdihydroalprenolol binding to beta1- and beta2-noradrenergic receptors in brain, heart, and lung membranes.

(+/-)-3HEpinephrine binds to beta-receptors in calf cerebellar and rat lung membranes in the presence of 1.0 mM pyrocatechol and 1.0 microM phentolamine, with dissociation constants at 4 degrees C of 11 nM and 24 nM, respectively. (+/-)-3HEpinephrine associates to equilibrium within 20 min in both tissues, and over 50% of the binding is rapidly dissociable. Inhibition of binding by agonists and antagonists is highly stereoselective, and the structure-activity relationships of adrenergic agents in inhibiting (+/-)-3Hepinephrine binding suggest an interaction with beta2 type noradrenergic receptors. (-)-Isoproterenol has an apparent Ki of 2 nM, (-)-epinephrine is 1.5 to 3 times weaker, and (-)-norepinephrine is 30 to 60 times weaker. Salbutamol and terbutaline, selective beta2-agonists, are potent inhibitors of binding, as are several nonspecific antagonists. Properties of the sites labeled by (+/-)-3Hepinephrine in calf cerebellum and rat lung are closely similar. (-)-3HDihydroalprenolol binding in calf cerebellum and rat lung also shows beta2 characteristics. Antagonists have similar potencies in inhibiting (-)-3Hdihydroalprenolol and (+/-)-3Hepinephrine binding in both tissues, but agonists are in general more potent inhibitors of (+/-)-3Hepinephrine. Sodium and lithium selectively lower the affinity of (+/-)-3Hepinephrine at its binding sites and the affinities of agonists, but not antagonists, at the (-)-3Hdihydroalprenolol site. Specific (+/-)-3Hepinephrine binding was not detectable in calf cortex and rat heart, where (-)-3Hdihydroalprenolol binding suggests a beta1-receptor. A physiological significance of (+/-)-3Hepinephrine binding is suggested by the strong correlation for agonists and antagonists between affinities in inhibiting binding, and in stimulating or inhibiting a beta-receptor-coupled adenylate cyclase in frog erythrocytes.