Role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro.

Tomonori Yamanishi, Christopher R Chapple, Kosaku Yasuda, Ken-Ichiro Yoshida, Russell Chess-Williams

Department of Urology, Dokkyo University, Japan. yamanish@dokkyomed.ac.jp

Neurourology and urodynamics 2003

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To investigate the role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro. Longitudinal strips of trigonal muscle were isolated, and the mucosa and serosa removed. Tissues were precontracted with KCl, and beta-adrenoceptor agonists (isoprenaline or salbutamol) were added cumulatively, and concentration-relaxation curves (CRCs) were obtained. CRCs to agonists were obtained in the absence and presence of antagonists and antagonist affinity values were calculated. Isoprenaline (non-selective beta-agonist) relaxed with high potency (pEC(50) = 7.2). Propranolol antagonized CRCs to isoprenaline with a high affinity (apparent pK(B) = 8.8), but the Schild plot had a slope significantly (P < 0.01) less than unity (0.61), suggesting that responses were mediated by more than one beta-adrenoceptor subtype. CGP20712A (beta(1)-antagonist) antagonized responses to isoprenaline with a low affinity (apparent pK(B) = 5.13), indicating beta(1)-adrenoceptors did not participate in the response. The affinity of ICI118551 (beta(2)-antagonist) for antagonism of responses to isoprenaline was also relatively low (apparent pK(B) = 6.9), and the Schild slopes were significantly (P < 0.01) less than unity (0.58). SR59230A (beta(3)-antagonist) antagonized CRCs to isoprenaline with a relatively low affinity (apparent pK(B) = 7.5), and with a Schild slope significantly (P < 0.01) less than unity (0.86), indicating that responses may be mediated by more than one beta-adrenoceptor subtype. In contrast to that observed with isoprenaline, the beta(2)-adrenoceptor selective agonist salbutamol induced relaxation with a relatively low potency (pEC(50) = 6.6) and with maximum responses of 80% of that to isoprenaline. ICI118551 competitively antagonized (Schild plot of unity) responses to salbutamol with a high affinity (pA2 = 8.3). These data suggest that beta-adrenoceptor mediated responses to isoprenaline of the bladder trigone are mediated via both the beta(2)- and beta(3)-adrenoceptor subtypes whilst responses to salbutamol appear to be mediated only via the beta(2)-adrenoceptor. Copyright 2003 Wiley-Liss, Inc.

Citation

Tomonori Yamanishi, Christopher R Chapple, Kosaku Yasuda, Ken-Ichiro Yoshida, Russell Chess-Williams. Role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro. Neurourology and urodynamics. 2003;22(4):338-42