1568 OXYTOCIN PRODUCES CONTRACTION OF HUMAN ISOLATED PROSTATE, AN EFFECT BLOCKED BY THE NOVEL AND SELECTIVE OXYTOCIN RECEPTOR ANTAGONIST GSK557296 POTENTIAL ROLE IN BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121568 OXYTOCIN PRODUCES CONTRACTION OF HUMAN ISOLATED PROSTATE, AN EFFECT BLOCKED BY THE NOVEL AND SELECTIVE OXYTOCIN RECEPTOR ANTAGONIST GSK557296 POTENTIAL ROLE IN BENIGN PROSTATIC HYPERPLASIA Celine Rouget, Moez Rekik, Philippe Camparo, Henry Botto, Pascal Rischmann, Philippe Lluel, Stefano Palea, Stewart W. McCallum, and Timothy D. Westfall Celine RougetCeline Rouget Toulouse, France More articles by this author , Moez RekikMoez Rekik 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 , Pascal RischmannPascal Rischmann Toulouse, France More articles by this author , Philippe LluelPhilippe Lluel Toulouse, France More articles by this author , Stefano PaleaStefano Palea Toulouse, France More articles by this author , Stewart W. McCallumStewart W. McCallum King of Prussia, PA More articles by this author , and Timothy D. WestfallTimothy D. Westfall Gladwyne, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1340AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Oxytocin (OT) concentrations have been shown to be elevated in prostatic tissue from patients with benign prostatic hyperplasia (BPH) suggesting that OT may play a role in the disease. Not only has OT been shown to play a role in prostate cell proliferation it may also produce contraction of the prostate through its specific receptor, however this has not been definitively demonstrated. Therefore the aim of the present study was to evaluate whether OT produces contraction of human isolated hyperplastic prostate and determine whether this response is mediated by specific OT receptors using the selective oxytocin receptor antagonist GSK557296. METHODS Prostatic tissue was obtained from 9 patients (65 ± 3 years old) undergoing prostatic adenomectomy for BPH. Strips were mounted under 1 g of initial tension. After 60 min of equilibration, strips were exposed to 30 μM norepinephrine (NE) to determine tissue viability. After wash-out and 60 min of re-equilibration, GSK557296 (0.1-1 μM) or tamsulosin (10 nM) were incubated for 60 min followed by a single concentration of OT (1 μM) or cumulative concentrations of NE (0.1-1000 μM), respectively. RESULTS In preliminary experiments it was determined that cumulative concentration response curves to OT were not possible due to desensitization. In subsequent experiments, single applications of OT (0.1-1 μM) produced contractions of isolated prostate with similar efficacy and potency to equivalent concentrations of NE. At 1 μM, OT induced contractions equal to 12.5% of the maximal contraction to 30 μM NE. GSK557296 inhibited contractions induced by 1 μM OT in a concentration-dependent manner. Responses to OT were reduced 33% in the presence of GSK557296 at 30 nM. At higher concentrations (100 nM and 1 μM), GSK557296 inhibited OT-induced contractions by ≥ 60%. NE (0.1 – 1000 μM) induced concentration-dependent contractions with an EC50 value of approximately 10 μM. Tamsulosin (10 nM) decreased the potency and efficacy of NE with an estimated pKB value of 9.19, similar to that previously reported. CONCLUSIONS This is the first definitive demonstration of a contractile effect of OT in human prostatic tissue through specific OT receptors. These effects of OT could contribute to symptoms of BPH. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e635 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Celine Rouget Toulouse, France More articles by this author Moez Rekik 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 Pascal Rischmann Toulouse, France More articles by this author Philippe Lluel Toulouse, France More articles by this author Stefano Palea Toulouse, France More articles by this author Stewart W. McCallum King of Prussia, PA More articles by this author Timothy D. Westfall Gladwyne, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...