You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20101405 EVALUATING THE SIGNIFICANCE OF THE CYCLIC AMP-MEDIATED SIGNALLING IN THE CONTROL OF SMOOTH MUSCLE OF THE HUMAN PROSTATE – A FUNCTIONAL AND BIOCHEMICAL STUDY George Kedia, Dietmar Schönfeld, Michael Seidler, Markus Kuczyk, and Stefan Ückert George KediaGeorge Kedia More articles by this author , Dietmar SchönfeldDietmar Schönfeld More articles by this author , Michael SeidlerMichael Seidler More articles by this author , Markus KuczykMarkus Kuczyk More articles by this author , and Stefan ÜckertStefan Ückert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1097AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Basic and clinical research on the use of phosphodiesterase (PDE) inhibitors to treat lower urinary tract symptomatology (LUTS) suggestive of benign prostatic hyperplasia (BPH) has been focused mainly on the nitric oxide (NO)/cyclic GMP pathway and the cyclic GMP-specific PDE5. Up until today, only a very few studies have addressed the potential significance of the cyclic AMP-dependent signal transduction and related proteins (for example the PDE4) in the control of the function of the human prostate. This prompted us to evaluate further the significance of the cyclic AMP signalling in the mechanism of prostate smooth muscle relaxation. METHODS Human prostate tissue from the transition zone was obtained from male patients who had undergone pelvic surgery. Using the organ bath technique, the effects of the PDE4 inhibitors rolipram, Ro 20-1724 and ZK 803616 on the tension induced by norepinephrine (NE, 40 μM) of isolated prostate tissue were investigated in comparison to the PDE5 inhibitors sildenafil citrate, DASPP and MSPP, and BAY 13-1197, a NO-independent activator of the soluble guanylyl cyclase (1 nM - 10 μM each). By means of chromatographic techniques, total PDE activity was isolated from the microsomal fraction prepared from rough homogenates of specimens taken from the transition zone and subjected to biochemical analysis. RESULTS In the organ bath experiments, rolipram, Ro 20-1724 and ZK 803616 dose-dependently reversed the tension induced by NE of the isolated prostate tissue by 32%, 59%, and 53%, respectively. Thus, the PDE4 inhibitors were as effective as MSPP (54%) and more effective than BAY 13-1197 (18%), sildenafil (17%), and DASPP (14%). Only a single peak of PDE activity was isolated from the microsomal fraction. This activity was suggestive of representing PDE4 since it was sensitive to increasing concentrations (0.01 μM - 100 μM) of papaverine (non-specific PDE inhibitor), and the PDE4 inhibitors rolipram and Ro 20-1724. CONCLUSIONS Our results present evidence for a significance of the cyclic AMP signalling in controlling prostate smooth muscle function. These findings might be of importance for the identification of new drug options to treat of symptoms of the benign prostatic syndrome (BPS). Hannover, Germany© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e542 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information George Kedia More articles by this author Dietmar Schönfeld More articles by this author Michael Seidler More articles by this author Markus Kuczyk More articles by this author Stefan Ückert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...