title: Comparison between CL-316243- and CGP-12177A-induced relaxations in isolated canine ureter.
abstract: We compared the effects of CL-316243, a selective beta(3)-adrenoceptor agonist, and CGP-12177A, a nonconventional partial beta-adrenoceptor agonist, on the KCl-induced contraction in the isolated canine ureter. CL-316243 concentration dependently relaxed the ureteral contraction, the pD(2) value being 7.75 +/- 0.11. This relaxation was competitively antagonized by the selective beta(3)-adrenoceptor antagonist SR58894A and by the nonselective beta-adrenoceptor antagonist bupranolol, their pA(2) values being 7.08 +/- 0.08 and 6.43 +/- 0.09, respectively. CGP-12177A concentration dependently reduced the KCl-induced contraction, the pD(2) value being 6.30 +/- 0.25. Even at 1 x 10(-5) mol/l, CGP-20712A (a selective beta(1)- adrenoceptor antagonist) did not shift the concentration-response curves for CL-316243 or CGP-12177A. SR58894A did not induce a parallel rightward shift in the concentration-response curve for CGP-12177A, but bupranolol did produce such a shift, pA(2) and slope values in the Schild plot being 7.15 +/- 0.77 and 0.60 +/- 0.15, respectively. Hence, the competition characteristics for SR58894A and bupranolol differed between the CL- 316243-induced and CGP-12177A-induced relaxations. Our results suggest that CGP-12177A produces ureteral relaxation in the dog via an atypical beta-adrenoceptor (possibly, an atypical site/state of the beta(3)-adrenoceptor) as well as via the typical beta(3)-adrenoceptor.
authors.affiliation: Pharmacology Research R&D, Kissei Pharmaceutical Co Ltd, Nagano, Japan. yoshitaka_tomiyama@pharm.kissei.co.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Masami
authors.initials: M
authors.lastname: Kojima
authors.forename: Masuo
authors.initials: M
authors.lastname: Akahane
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013379:Substrate Specificity; D014513:Ureter / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C033394:CGP 12177