Jpn. J. Pharmacol. 84 (3), 287-292 (2000)

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

Takahiro Horinouchi and Katsuo Koike*

Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
*Corresponding author.╩╩FAX:+81-47-472-1419

Abstract: The properties of the b1-/b2-adrenoceptor partial agonist carteolol were investigated in atypical b-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 b1-adrenoceptor antagonist atenolol (100╩mM) and the selective b2-adrenoceptor antagonist butoxamine (100╩mM) 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╩mM) and butoxamine (100╩mM), the non-selective b1-, b2- and b3-adrenoceptor antagonist (▒)-bupranolol (10-100╩mM) caused a concentration-dependent rightward 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╩mM) weakly but significantly antagonized the relaxant responses to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective b3-adrenoceptor agonist BRL37344 ((R*,R*)-(▒)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium salt) and a non-conventional partial b3-adrenoceptor agonist (▒)-CGP12177A ([4-[3-[(1,1-dimethylethyl)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 b-adrenoceptors in the guinea pig gastric fundus.

Keywords: Carteolol, Partial agonist, Atypical b-adrenoceptor, b3-Adrenoceptor, Guinea pig gastric fundus

Copyrightę The Japanese Pharmacological Society 2000

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