Partial Agonistic Properties of (±)-Pindolol at Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus

Abstract

(±)-Pindolol ([1-(1H-indol-4-yloxy)-3-[(1-methylethyl)- amino]-2-propanol)]) is a partial agonist at atypical β-adrenoceptors in the guinea pig gastric fundus. (±)-Pindolol induced concentration-dependent relaxation in this tissue. However, the relaxant responses of (±)-pindolol were not antagonized by a combination of the selective β₁-adrenoceptor antagonist atenolol (10^–4 mol/l) and the selective β₂-adrenoceptor antagonist butoxamine (10^–4 mol/l). In the presence of both atenolol and butoxamine, the nonselective β₁-, β₂- and β₃-adrenoceptor antagonist (±)-bupranolol (10^–5–10^–4 mol/l) caused a concentration-dependent rightward shift of the concentration-response curves for (±)-pindolol. Schild plot analyses of (±)-bupranolol against (±)-pindolol gave the pA₂ value of 5.46 ± 0.03 and Schild slope was not significantly different from unity. Furthermore, (±)-pindolol (10^–5 mol/l) weakly but significantly antagonized the relaxant responses to catecholamines ((–)-isoprenaline, (–)-noradrenaline and (–)-adrenaline), a selective β₃-adrenoceptor agonist BRL37344 ((R*,R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium salt) and a nonconventional partial β₃-adrenoceptor agonist (±)-CGP12177A ([4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride). These results suggest that (±)-pindolol acts as a partial agonist at atypical β-adrenoceptors in the guinea pig gastric fundus.