High potency congeners of isoproterenol. Binding to beta-adrenergic receptors, activation of adenylate cyclase and stimulation of intracellular cyclic AMP synthesis.
The potency of a p-toluide derivative and a p-trifluoromethyl derivative of isoproterenol on the beta1 receptor of turkey erythrocytes and on the beta2 receptor of S49 lymphoma cells was measured in comparison with isoproterenol. Binding assays showed that the p-trifluoromethyl derivative possessed an affinity for the receptor, which was two hundred times higher than that of isoproterenol, in the case of turkey erythrocytes, and sixty times higher in the case of the S49 cells. By measuring the Kact of adenylate cyclase, the activity of the p-trifluoromethyl derivative was thirty to forty times higher than that of isoproterenol for the turkey erythrocyte membrane as well as for the S49 lysed cells. In stimulation of intracellular cyclic AMP accumulation, the Kact showed that the p-trifluoromethyl derivative was forty and twenty times more active than isoproterenol in turkey erythrocytes and in S49 cells, respectively. The p-toluide derivative gave similar results. The superior affinity of the above isoproterenol congeners for both beta 1 and beta 2 adrenergic receptors makes these compounds excellent candidates for use as labeled agonist ligands in studies of beta receptors. The possibility is discussed that the relatively large substituent on the amino group of the catecholamine congeners might perhaps bind to lipids associated with the receptor.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000201:enzymology; D007545:Isoproterenol / Q000031:analogs & derivatives* / Q000378:metabolism; D008223:Lymphoma / Q000201:enzymology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014422:Turkeys
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol