BINDING OF A CATECHOL DERIVATIVE OF DENOPAMINE (T-0509) AND N-TERT-BUTYLNORADRENALINE (COLTEROL) TO BETA(1)-ADRENOCEPTOR AND BETA(2)-ADRENOCEPTOR

The affinities for beta-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamin e) and colterol (N-tert-butylnoradrenaline; Col) were ere compared wit h those of other beta-agonists using a binding assay method. Specific binding of [H-3]dihydroalprenolol (H-3-DHA) to guinea pig left ventric ular and lung membranes was saturable, and Scatchard and Hill analyses suggested that H-3-DHA bound to both membranes with a single populati on of binding sites with no binding site cooperativity. Addition of 5' -guanylylimidodiphosphate (GppNHp, 30 mu M) led to a rightward shift o f the H-3-DHA binding displacement curves of T-0509 and Col in both me mbranes, and the degree of shift was similar to that of full agonists such as isoproterenol (Iso), adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered to be full agonists at both b eta(1)- and beta(2)-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both beta(1)- and beta(2)-adrenoceptors, and T-0509, like denopamine, was as selective for the beta(1)-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the b eta(2)-subtype than Adr (4.5-fold compared with Iso).