Differentiation of binding sites of CGP12177, a beta(3)-adrenoceptor partial agonist, and carteolol, a beta(1)/beta(2)-adrenoceptor partial agonist, to the beta-adrenoceptors in guinea-pig taenia caecum

Differentiation of binding sites of CGP 12177 and carteolol to the beta-adrenoceptors in the guinea-pig taenia caecum was investigated. Carteolol and CGP12177 competitively antagonized the relaxation responses to isoprenaline, and the pA(2) values were 9.87 and 9.33, respectively. Butoxamine, a beta(2)-selective antagonist, caused competitive antagonism of the relaxant responses to carteolol, and the pA(2) value for butoxamine was 6.22. However, butoxamine (10(-4) M) did not significantly affect the relaxant responses to CGP12177. CGP12177 caused competitive antagonism of the relaxant responses to carteolol, and the pA(2) value for CGP12177 was 9.32. However, carteolol (10(-6) M) did not significantly affect the relaxant responses to CGP12177. The competitive inhibition curve for specific binding of 50 nM [H-3]befunolol by carteolol showed a biphasic shape, although the curve by CGP12177 was monophasic. Moreover, the competitive inhibition curve for specific binding of 100 nM [H-3]CGP12177 by CGP12177 showed a biphasic shape, although the curve by carteolol indicated partial inhibition. These results suggest that the low affinity site of beta-adrenoceptor and beta(3)-adrenoceptors are different from each other.