Partial Agonistic Effects of Carteolol on Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus

The properties of the beta1-/beta2-adrenoceptor partial agonist carteolol were investigated in atypical beta-adrenoceptors on the guinea pig gastric fundus. Carteolol induced concentration-dependent relaxation in this tissue (pD2 = 5.55, intrinsic activity = 0.94). However, a combination of the selective beta1-adrenoceptor antagonist atenolol (100 microM) and the selective beta2-adrenoceptor antagonist butoxamine (100 microM) produced only small rightward shifts in the concentration-response curves of carteolol in the gastric fundus (pD2 = 4.91, intrinsic activity = 0.94). In the presence of both atenolol (100 microM) and butoxamine (100 microM), the non-selective beta1-, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol (10-100 microM) caused a concentration-dependent right-ward shift of the concentration-response curves for carteolol in the guinea pig gastric fundus. Schild plot analyses of the effects of (+/-)-bupranolol against carteolol gave the pA2 value of 5.29 and the Schild slope was not significantly different from unity. Furthermore, carteolol (10 microM) weakly but significantly antagonized the relaxant responses to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective beta3-adrenoceptor agonist BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxy-acetic acid sodium salt) and a non-conventional partial beta3-adrenoceptor agonist (+/-)-CGP12177A ([4-[3-[(1,1dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride) in the guinea pig gastric fundus. These results suggest that the partial agonistic effects of carteolol are mediated by atypical beta-adrenoceptors in the guinea pig gastric fundus.