In vitro determination of the ability of drugs to bind to adrenergic receptors.
Alpha- and beta-adrenergic receptors were studied by measuring the binding of 3H-dihydroergocryptine and 3H-dihydroalprenolol, respectively, to membranes prepared from homogenized rabbit iris--ciliary bodies. The binding of 3H-dihydroergocryptine appears to be specific for alpha-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: phentolamine greater than epinephrine greater than or equal to norepinephrine greater than or equal to isoproterenol = propranolol. The binding of 3H-dihydroalprenolol appears to be specific for beta-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: propranolol greater than or equal to isoproterenol greater than or equal to epinephrine greater than norepinephrine greater than or equal to phentolamine. Clonidine and dopamine bind to the alpha-adrenergic receptor but have little activity at the beta-adrenergic receptor. Timolol, d-isoproterenol, and dipivalyl epinephrine bind to the beta-adrenergic receptor but have little activity at the alpha-adrenergic receptor. The results demonstrate that in vitro binding assays for alpha- and beta-adrenergic receptors are useful for studying the mechanism of drug action.
D000526:Alprenolol / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002924:Ciliary Body / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004088:Dihydroergotoxine / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013999:Timolol / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004088:Dihydroergotoxine; D013999:Timolol; D000526:Alprenolol; D011433:Propranolol; D007545:Isoproterenol; D003000:Clonidine; D004298:Dopamine; D004837:Epinephrine; D010646:Phentolamine