Modulation of nerve-evoked contractions by β3-adrenoceptor agonism in human and rat isolated urinary bladder

Activation of beta(3)-adrenoceptors has been shown to have a direct relaxant effect on urinary bladder smooth muscle from both rats and humans, however there are very few studies investigating the effects of 133-adrenoceptor agonists on nerve-evoked bladder contractions. Therefore in the current study, the role of I33-adrenoceptors in modulating efferent neurotransmission was evaluated. The effects of 133adrenoceptor agonism on neurogenic contractions induced by electrical field stimulation (EFS) were compared with effects on contractions induced by exogenous acetylcholine (Ach) and ceI3-methylene adenosine triphosphate (otp-meATP) in order to determine the site of action. Isoproterenol inhibited EFS-induced neurogenic contractions of human bladder (pD(2) = 6.79; E-max = 65%). The effect of isoproterenol was selectively inhibited by the 133-adrenoceptor antagonist L-748,337 (pICB = 7.34). Contractions induced by exogenous Ach (0.5-1 mu M) were inhibited 25% by isoproterenol (3 mu M) while contractions to 10 Hz in the same strip were inhibited 67%. The selective 133-adrenoceptor agonist CL-316,243 inhibited EFS-induced neurogenic contractions of rat bladder (pD2 = 7.83; E-max = 65%). The effects of CL-316,243 were inhibited in a concentration dependent manner by L-748,337 (PA(2) = 6.42). Contractions induced by exogenous Ach and alpha beta-meATP were significantly inhibited by CL-316,243, 29% and 40%, respectively. These results demonstrate that the activation of beta(3)-adrenoceptors inhibits neurogenic contractions of both rat and human urinary bladder. Contractions induced by exogenously applied parasympathetic neurotransmitters are also inhibited by beta(3)-agonism however the effect is clearly less than on neurogenic contractions (particularly in human), suggesting that in addition to a direct effect on smooth muscle, activation of prejunctional beta(3)-adrenoceptors may inhibit neurotransmitter release. (C) 2013 Elsevier Ltd. All rights reserved.