You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2010190 STIMULATION OF β3-ADRENOCEPTORS INHIBITS EFS-INDUCED CONTRACTIONS OF HUMAN ISOLATED URINARY BLADDER Moèz Rekik, Céline Rouget, Philippe Camparo, Henry Botto, Philippe Lluel, Timothy Westfall, and Stefano Palea Moèz RekikMoèz Rekik Toulouse, France More articles by this author , Céline RougetCéline Rouget Toulouse, France More articles by this author , Philippe CamparoPhilippe Camparo Suresnes, France More articles by this author , Henry BottoHenry Botto Suresnes, France More articles by this author , Philippe LluelPhilippe Lluel Toulouse, France More articles by this author , Timothy WestfallTimothy Westfall Toulouse, France More articles by this author , and Stefano PaleaStefano Palea Toulouse, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.246AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Activation of β-adrenoceptors (β-AR) has been shown to produce relaxation of pre-contracted urinary bladder smooth muscle suggesting that β-AR agonism could promote relaxation of basal tension during urine storage. However, very little is known about how β-AR agonism affects neuronal efferent activity. The aim of the present study was to investigate the effect of β-AR agonism on neurogenic contractions of human isolated detrusor and the β-ARs involved. METHODS Detrusor smooth muscle strips devoid of urothelium were obtained from 11 patients (72 ± 3 years old, 10 male and 1 female) undergoing cystectomy due to bladder cancer. Strips were mounted under 1 g of initial tension and electrical field stimulation (EFS) applied using the following parameters: maximal current, frequency of 10 Hz, square pulses of 0.1 ms, trains of 5 s every min. L748,337 (β3-AR antagonist at 0,3, 1 and 3 μM), ICI118,551 (β2-AR antagonist at 30 and 100 nM) or vehicle were added, followed 20 min later by a cumulative concentration-response curves to a β-AR agonists (isoproterenol, L755,507 or CL316,243). Responses are expressed as % variation from basal EFS-induced contractions. RESULTS Isoproterenol concentration-dependently inhibited TTX-sensitive EFS-induced contractions of human bladder smooth muscle strips with an EC50 value of 0.19 ± 0.11 μM and an Emax value of 66.6 ± 3.9% at 30 μM. In contrast L755,507 and CL316,243 decreased EFS-induced contractions by only 30.0 ± 8.9 % at 10 μM and 20.8 ± 3.5 % at 30 μM, respectively. The β2-AR antagonist, ICI118,551 at 30 and 100 nM had no effect on the response to isoproterenol. However, the β3-AR antagonist L748,337 induced a concentration-dependent rightward shift of the isoproterenol response without affecting the maximal effect. Schild plot analysis revealed a pA2 value of 7.37 and a slope of 1.07 ± 0.19 indicating competitive antagonism. CONCLUSIONS While it is well known that stimulation of β-ARs produces relaxation of basal tension and carbachol pre-contracted detrusor muscle, there are very few reports on the effect of β-AR agonists on EFS induced-responses. Here, we clearly demonstrate that isoproterenol is able to significantly inhibit EFS-induced contractions of human detrusor muscle through activation of β3-ARs. It remains to be determined if this effect is pre- or post-junctional, however the results suggest that in addition to producing relaxation of basal tension during urine storage, β3-AR agonism might inhibit neuronally mediated non-voiding and voiding contractions. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e75-e76 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Moèz Rekik Toulouse, France More articles by this author Céline Rouget Toulouse, France More articles by this author Philippe Camparo Suresnes, France More articles by this author Henry Botto Suresnes, France More articles by this author Philippe Lluel Toulouse, France More articles by this author Timothy Westfall Toulouse, France More articles by this author Stefano Palea Toulouse, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...