title: Differentiation of binding sites of CGP12177, a beta 3-adrenoceptor partial agonist, and carteolol, a beta 1/beta 2-adrenoceptor partial agonist, to the beta-adrenoceptors in guinea-pig taenia caecum.
abstract: Differentiation of binding sites of CGP12177 and carteolol to the beta-adrenoceptors in the guinea-pig taenia caecum was investigated. Carteolol and CGP12177 competitively antagonized the relaxation responses to isoprenaline, and the pA2 values were 9.87 and 9.33, respectively. Butoxamine, a beta 2-selective antagonist, caused competitive antagonism of the relaxant responses to carteolol, and the pA2 value for butoxamine was 6.22. However, butoxamine (10(-4) M) did not significantly affect the relaxant responses to CGP12177. CGP12177 caused competitive antagonism of the relaxant responses to carteolol, and the pA2 value for CGP12177 was 9.32. However, carteolol (10(-6) M) did not significantly affect the relaxant responses to CGP12177. The competitive inhibition curve for specific binding of 50 nM [3H]befunolol by carteolol showed a biphasic shape, although the curve by CGP12177 was monophasic. Moreover, the competitive inhibition curve for specific binding of 100 nM [3H]CGP12177 by CGP12177 showed a biphasic shape, although the curve by carteolol indicated partial inhibition. These results suggest that the low affinity site of beta-adrenoceptor and beta 3-adrenoceptors are different from each other.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: I
authors.initials: I
authors.lastname: Takayanagi
authors.forename: M
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002354:Carteolol / Q000378:metabolism / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014316:Tritium
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014316:Tritium; C006034:befunolol; D002354:Carteolol; C033394:CGP 12177