(+/-)-Pindolol acts as a partial agonist at atypical beta-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 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 beta1- and beta2-adrenoceptor antagonist (+/-)-propranolol (1 microM). In the presence of (+/-)-propranolol (1 microM), the non-selective beta1-, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol (30 microM) induced a rightward shift of the concentration-response curves for (+/-)-pindolol (apparent pA2 = 5.41 +/- 0.06). In the presence of (+/-)-propranolol, (+/-)-pindolol (10 microM) weakly but significantly antagonized the relaxant effects to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective beta3-adrenoceptor agonist BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl) amino]propyl]phenoxyacetic acid sodium salt) and a non-conventional partial beta3-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.
Horinouchi
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
Koike
K
K
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010869:Pindolol / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C057368:BRL 37344; D002046:Bupranolol; D011433:Propranolol; D010869:Pindolol; C033394:CGP 12177