Pharmacological analysis of atypical beta-adrenoceptors in the guinea pig gastric fundus using the beta(3)-adrenoceptor antagonist bupranolol.
Atypical beta-adrenoceptor-mediated relaxations to catecholamines (isoprenaline, noradrenaline and adrenaline) and beta(3)-adrenoceptor agonists, BRL37344 [(R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]-propyl]phen oxyacetic acid sodium salt] and CGP12177A [(-)-4-(3-t-butylamino-2-hydroxy- propoxy)benzimidazol-2-one] in guinea pig gastric fundus were investigated. The five agonists induced concentration-dependent relaxation of the gastric fundus. In the presence of both atenolol and butoxamine only small rightward shifts of the concentration-response curves to these agonists were observed. Under this condition, however, bupranolol caused a concentration-dependent rightward shift of the concentration-response curve to catecholamines and beta(3)-adrenoceptor agonists. Schild plot analyses of bupranolol against these agonists gave pA(2) values of 6.08 (isoprenaline), 6. 04 (noradrenaline), 5.90 (adrenaline), 6.50 (BRL37344) and 5.80 (CGP12177A), respectively. These results clearly suggest that the existence of functional atypical beta-adrenoceptors in the guinea pig gastric fundus and the relaxation of these agonists in this tissue are mediated via atypical beta-adrenoceptors.
Horinouchi
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Koike
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002046:Bupranolol / Q000494:pharmacology*; D002078:Butoxamine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; D002078:Butoxamine; D001262:Atenolol; C057368:BRL 37344; D002046:Bupranolol; D007545:Isoproterenol; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine