Binding of a Catechol Derivative of Denopamine (T-0509) and N-tert-Butylnoradrenaline (Colterol) to β₁-and β₂-Adrenoceptors

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The affinities for β-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N-tert-butylnoradrenaline ; Col) were compared with those of other β-agonists using a binding assay method. Specific binding of [³H] dihydroalprenolol (³H-DHA) to guinea pig left ventricular and lung membranes was saturable, and Scatchard and Hill analyses suggested that ³H-DHA bound to both membranes with a single population of binding sites with no binding site cooperativity. Addition of 5'-guanylyl-imidodiphosphate (GppNHp, 30μM) led to a rightward shift of the ³H-DHA binding displacement curves of T-0509 and Col in both membranes, 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 β₁-and β₂-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both β₁-and β₂-adrenoceptors, and T-0509, like denopamine, was as selective for the β₁-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the β₂-subtype than Adr (4.5-fold compared with Iso).