(±)-Pindolol Acts as a Partial Agonist at Atypical β -Adrenoceptors in the Guinea Pig Duodenum

Abstract

The agonistic and antagonistic effects of (±)-pindolol (1-(1H-indol-4-yloxy)-3-[(1-methyleth-yl)amino]-2-propanol) were estimated to clarify whether (±)-pindolol acts as a partial agonist on atypical β-adrenoceptors in the guinea pig duodenum. (±)-Pindolol induced concentration-dependent relaxation with a pD2 value of 5.10 ± 0.03 and an intrinsic activity of 0.83 ± 0.03. However, the relaxations to (±)-pindolol were not antagonized by the non-selective β1- and β2-adrenoceptor antagonist (±)-propranolol (1 μM). In the presence of (±)-propranolol (1 μM), the non-selective β1-, β2 and β3-adrenoceptor antagonist (±)-bupranolol (30 μM) induced a rightward shift of the concentration-response curves for (±)-pindolol (apparent pA2 = 5.41 ± 0.06). In the presence of (±)-propranolol, (±)-pindolol (10 μM) weakly but significantly antagonized the relaxant effects 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 non-conventional partial β3-adrenoceptor agonist (±)-CGP12177A ([4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride). These results demonstrate that (±)-pindolol possesses both agonistic and antagonistic effects on atypical β-adrenoceptors in the guinea pig duodenum.