Partial agonist activity of carteolol on atypical beta-adrenoceptors in the guinea pig duodenum.
The partial agonist activities of carteolol were investigated on atypical beta-adrenoceptors of duodenum on the guinea pig. Carteolol produced a concentration-dependent relaxation of the guinea pig duodenum (pD(2)=4.85), which was not significantly affected by propranolol (1 microM). In the presence of propranolol (1 microM), however, the non-selective beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonist, bupranolol (30 microM), caused a rightward shift of the concentration-response curves for carteolol (apparent pA(2)=5.31). Moreover, carteolol (10 microM) weakly, but significantly, antagonized the relaxations in response to catecholamines (isoprenaline, noradrenaline and adrenaline), to a selective beta(3)-adrenoceptor agonist, (R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]pheno xyacetic acid sodium salt (BRL37344), and to a non-conventional partial beta(3)-adrenoceptor agonist, [4-[3-[(1, 1-dimethylethyl)amino]-2-hydroxypropoxy]-1, 3-dihydro-2H-benzimidazol-2-one] hydrochloride (CGP12177A), also in the guinea pig duodenum (apparent pA(2)=5.77, 5.92, 6.05, 6.56 and 5. 58, respectively). These results suggest that the partial agonist effects of carteolol are mediated by atypical beta-adrenoceptors in the guinea pig duodenum.
Horinouchi
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1, Miyama, Chiba 274-8510, Funabashi, Japan.
Koike
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D002354:Carteolol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C057368:BRL 37344; D002046:Bupranolol; D002354:Carteolol; D011433:Propranolol; D007545:Isoproterenol; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine