Effect of SR59230A on atypical beta-adrenoceptor mediating relaxation in the Guinea Pig gastric fundus.

The purpose of the present study was to clarify whether atypical beta-adrenoceptors which presented in the guinea pig gastric fundus are beta(3)-adrenoceptors or putative beta(4)-adrenoceptors. In the presence of both the selective beta(1)-adrenoceptor antagonist atenolol (10(-4) mol/l) and the selective beta(2)-adrenoceptor antagonist butoxamine (10(-4) mol/l), the selective beta(3)-adrenoceptor antagonist SR59230A caused a concentration-dependent rightward shift of the concentration-response curve to catecholamines (isoprenaline, noradrenaline and adrenaline) and beta(3)-adrenoceptor agonists (BRL37344 and CGP12177A) in the guinea pig gastric fundus. Schild plot analyses of SR59230A against these agonists gave pA(2) values of 7.35 +/- 0.03 (isoprenaline), 7.26 +/- 0.04 (noradrenaline), 7.26 +/- 0.05 (adrenaline), 7.79 +/- 0.03 (BRL37344) and 6.74 +/- 0.03 (CGP12177A), respectively, and all Schild slopes were not significantly different from unity. These results suggest that atypical beta-adrenoceptors mediating relaxant responses of these agonists in the guinea pig gastric fundus are beta(3)-adrenoceptors rather than putative beta(4)-adrenoceptors. Copyright 2001 S. Karger AG, Basel.