Comparison between CL-316243- and CGP-12177A-Induced Relaxations in Isolated Canine Ureter

We compared the effects of CL-316243, a selective β3-adrenoceptor agonist, and CGP-12177A, a nonconventional partial β-adrenoceptor agonist, on the KCl-induced contraction in the isolated canine ureter. CL-316243 concentration dependently relaxed the ureteral contraction, the pD2 value being 7.75 ± 0.11. This relaxation was competitively antagonized by the selective β3-adrenoceptor antagonist SR58894A and by the nonselective β-adrenoceptor antagonist bupranolol, their pA2 values being 7.08 ± 0.08 and 6.43 ± 0.09, respectively. CGP-12177A concentration dependently reduced the KCl-induced contraction, the pD2 value being 6.30 ± 0.25. Even at 1 × 10–5 mol/l, CGP-20712A (a selective β1- 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, pA2 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 β-adrenoceptor (possibly, an atypical site/state of the β3-adrenoceptor) as well as via the typical β3-adrenoceptor.