You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-Neurogenic Voiding Dysfunction II1 Apr 20101680 MODULATION OF G-PROTEIN-COUPLED RECEPTOR (GPCR) SIGNAL TRANSDUCTION PATHWAYS BY CHANGES OF RHO-KINASE GENE EXPRESSION IN HUMAN DETRUSOR TISSUE UNDER VARIOUS CONDITIONS OF BLADDER FUNCTION Christian Hampel, Christoph Wiesner, Joachim W. Thüroff, and Jon Jones Christian HampelChristian Hampel More articles by this author , Christoph WiesnerChristoph Wiesner More articles by this author , Joachim W. ThüroffJoachim W. Thüroff More articles by this author , and Jon JonesJon Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1505AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Calcium-Sensitization is a novel concept to explain lower urinary tract symptoms (LUTS). The sustained smooth muscle contraction is dependent on the extent of myosin light chain (MLC) phosphorylation. GPCR-activated Rho-Kinase (ROCK) inhibits MLC-Phosphatase, thus leading to a larger amount of phosphorylated MLC with consecutive increase of contractility. In case of patients with LUTS refractory to common anticholinergic therapy, inhibition of Rho-Kinase could be a alternative pharmacological target. We investigate the molecular gene expression of ROCK in human detrusor tissue associated with BOO and/or DI. METHODS 73 detrusor specimens of prostate cancer patients were obtained from the anterior bladder wall during radical retropubic prostatectomy after the patients had undergone preoperative urodynamics. According to their specific urodynamic pattern, the patients were stratified into four groups (normal: n=23, obstructive non-irritative: n=25, irritative non-obstructive: n=10, obstructive irritative: n=15). After extraction of tissue RNA, a ROCK primer set was designed for 2-step Light Cycler PCR. The amplification values were equalized for RNA quality (GAPDH amplification as external standard), correlated with the specimen specific urodynamic group and statistically analysed (Mann-Whitney-U test). RESULTS ROCK gene expression did not differ significantly in the four groups (Tab. 1). When all irritative patients are compared to all non-irritative patients, the change in gene expression is not statistical significant (Irritative group: 0.63 ± 0.46, Non-Irritative group: 0.72 ± 0.48). Looking at obstruction only, there is no significant difference between the obstructive group (0.64 ± 0.5) and the non-obstructive group (0.72 ± 0.43). Tab. 1. Quantitative RT-PCR results of ROCK gene expression in correlation with urodynamic pattern (mean ± SD) ROCK/GAPDH amplification ratio Obstructive Urodynamics Non-obstructive Urodynamics Irritative Urodynamics 0.57±0.53 0.77±0.47 Non-irritative Urodynamics 0.71±0.52 0.7±0.43 CONCLUSIONS If an increased Ca2+ sensitization is postulated in LUTS patients, it is not caused by an upregulated ROCK gene expression. However, there are many more ways of regulating the balance between phosphorylated and unphosphorylated MLC. Moreover, an unchanged ROCK expression still promises a valuable target for future antagonist developments. Mainz, Germany© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e649 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian Hampel More articles by this author Christoph Wiesner More articles by this author Joachim W. Thüroff More articles by this author Jon Jones More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...