1574 C-JUN N-TERMINAL KINASE: A NEW MEDIATOR OF ALPHA1-ADRENOCEPTOR-INDUCED CONTRACTION IN THE HUMAN PROSTATE

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20111574 C-JUN N-TERMINAL KINASE: A NEW MEDIATOR OF ALPHA1-ADRENOCEPTOR-INDUCED CONTRACTION IN THE HUMAN PROSTATE Frank Strittmatter, Sebastian Walther, Christian Gratzke, Johanna Göttinger, Alexander Roosen, Boris Schlenker, Petter Hedlund, Karl-Erik Andersson, Christian Stief, and Martin Hennenberg Frank StrittmatterFrank Strittmatter Munich, Germany More articles by this author , Sebastian WaltherSebastian Walther Munich, Germany More articles by this author , Christian GratzkeChristian Gratzke Munich, Germany More articles by this author , Johanna GöttingerJohanna Göttinger Munich, Germany More articles by this author , Alexander RoosenAlexander Roosen Munich, Germany More articles by this author , Boris SchlenkerBoris Schlenker Munich, Germany More articles by this author , Petter HedlundPetter Hedlund Milan, Italy More articles by this author , Karl-Erik AnderssonKarl-Erik Andersson Winston Salem, NC More articles by this author , Christian StiefChristian Stief Munich, Germany More articles by this author , and Martin HennenbergMartin Hennenberg Munich, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1610AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Alpha1-adrenergic contraction of prostate smooth muscle is mediated by calcium- and Rho kinase-dependent mechanisms. In other types of smooth muscle, activation of c-Jun N-terminal kinase (JNK) may be another mechanism of α1-adrenoceptor-induced contraction. Objective: To investigate whether JNK participates in α1-adrenergic contraction of human prostate smooth muscle. METHODS Prostate tissue was obtained from patients undergoing radical prostatectomy. Effects of the JNK inhibitor SP600125 (50 μM) on phenylephrine-, noradrenaline-, and electric field stimulation- (EFS-) induced contraction were studied in myographic measurements. JNK activation by noradrenaline and phenylephrine was assessed by Western blot analyses with a phospho-specific antibody. Expression of JNK was studied by immunohistochemistry. RESULTS The JNK inhibitor SP600125 reduced phenylephrine- and noradrenaline-induced contraction of human prostate strips (p<0.05 vs. solvent at 3, 10, and 30 μM phenylephrine, n=6 patients; p<0.05 vs. solvent at 1, 3, 10, and 30 μM noradrenaline, n=7 patients). SP600125 reduced EFS-induced contraction of human prostate strips (before and after SP600125: p<0.05 for EFS at 8, 16, and 32 Hz; before and after solvent: p>0.05 for EFS at 8, 16, and 32 Hz; n=7 patients). Stimulation of prostate tissue with noradrenaline (30 μM, n=8 patients) or phenylephrine (10 μM, n=8 patients) in vitro resulted in activation of JNK. Immunohistochemical staining demonstrated expression of JNK in smooth muscle cells of human prostate tissue (n=5 patients). CONCLUSIONS α1-adrenergic contraction of prostate smooth muscle can be blocked by the JNK inhibitor SP600125. This demonstrates an involvement of JNK in α1-adrenergic prostate smooth muscle contraction. This mechanism may offer new targets for therapies of lower urinary tract symptoms. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e632 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Frank Strittmatter Munich, Germany More articles by this author Sebastian Walther Munich, Germany More articles by this author Christian Gratzke Munich, Germany More articles by this author Johanna Göttinger Munich, Germany More articles by this author Alexander Roosen Munich, Germany More articles by this author Boris Schlenker Munich, Germany More articles by this author Petter Hedlund Milan, Italy More articles by this author Karl-Erik Andersson Winston Salem, NC More articles by this author Christian Stief Munich, Germany More articles by this author Martin Hennenberg Munich, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...