(±)-pindolol acts as a partial agonist at atypical β-adrenoceptors in the guinea pig duodenum

The agonistic and antagonistic effects of(+/-)-pindolol(1-( 1H-indol-4-yloxy)-3- [(1-methylethyl)amino]-2-propanol) were estimated to clarify whether (+/-)-pindolol acts as a partial agonist on atypical beta -adrenoceptors in the guinea pig duodenum. (+/-)-Pindolol induced concentration-dependent relaxation with a pD(2) 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 beta (1)- and beta (2)-adrenoceptor antagonist (+/-)-propranolol (1 muM). In the presence of (+/-)-propranolol (1 muM), the non-selective beta (1)-, beta (2)- and beta (3)-adrenoceptor antagonist (+/-)-bupranolol (30 muM) induced a rightward shift of the concentration-response curves for (+/-)-pindolol (apparent pA(2) = 5.41 +/- 0.06). In the presence of (+/-)-propranolol, (+/-)-pindolol (10 muM) weakly but significantly antagonized the relaxant effects to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective beta (3)-adrenoceptor agonist BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2 amino] propyl]phenoxyacetic acid sodium salt) and a non-conventional partial pg-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 beta -adrenoceptors in the guinea pig duodenum.