MP19-09 NSC23766, A RAC GTPASE INHIBITOR, INHIBITS SMOOTH MUSCLE CONTRACTION IN THE HYPERPLASTIC HUMAN PROSTATE

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2014MP19-09 NSC23766, A RAC GTPASE INHIBITOR, INHIBITS SMOOTH MUSCLE CONTRACTION IN THE HYPERPLASTIC HUMAN PROSTATE Thomas Kunit, Andrea Schreiber, Christian Gratzke, Beata Rutz, Raphaela Waidelich, Frank Strittmatter, Christian G. Stief, and Martin Hennenberg Thomas KunitThomas Kunit More articles by this author , Andrea SchreiberAndrea Schreiber More articles by this author , Christian GratzkeChristian Gratzke More articles by this author , Beata RutzBeata Rutz More articles by this author , Raphaela WaidelichRaphaela Waidelich More articles by this author , Frank StrittmatterFrank Strittmatter More articles by this author , Christian G. StiefChristian G. Stief More articles by this author , and Martin HennenbergMartin Hennenberg More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.710AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate smooth muscle contraction may be critical for pathophysiology and therapy of lower urinary tract symptoms (LUTS) in patients with benign prostate hyperplasia (BPH). Although several options are available, medical therapy still remains a challenge, in particular with respect to the imminent demographic transition. Consequently, new strategies for inhibition of smooth muscle contraction in the lower urinary tract are of interest. Rac, a small monomeric GTPase, is an important regulator of smooth muscle tone outside the lower urinary tract. Here, we studied Rac inhibition and expression in the human prostate. METHODS Periurethral prostate tissues were obtained from patients undergoing radical prostatectomy (n=27). Effects of the Rac inhibitor, NSC23766 on adrenergic contraction were studied in the organ bath. Rac expression was examined by Western blot analysis, and immunofluorescence staining. RESULTS The α1-adrenoceptor agonist, phenylephrine (0.1-100 μM), induced concentration-dependent contractions of human prostate strips. NSC23766 (50 μM) inhibited phenylephrine-induced contractions (Fig.). This was significant at 0.3 μM phenylephrine (p<0.05 for NSC23766 vs. control), 1 μM (p<0.003), 3 μM (p<0.002), 10 μM (p<0.0002), and 30 μM (p<0.03). Similarly, NSC23766 (50 μM) inhibited noradrenaline-induced contractions (Fig.). This was significant at 0.3 μM (p<0.05) noreadrenaline, 1 μM (p<0.02), 3 μM (p<0.03), 10 μM (p<0.02), 30 μM (p<0.02), and 100 μM (p<0.03). In Western blot analysis revealed bands with the expected size for Rac1 in prostate tissue from each patient being included in this analysis. After immunofluorescence staining, immunoreactivity for Rac1 was observed in the prostate stroma, and in glands. Double labeling with calponin and pan-cytokeratin indicated localization in smooth muscle cells and in epithelial cells. CONCLUSIONS Rac is critical for prostate smooth muscle contraction. Regulation of smooth muscle tone in the lower urinary tract by Rac may be involved in pathophysiology of LUTS, and may represent a putative new target for therapy. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e192 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Thomas Kunit More articles by this author Andrea Schreiber More articles by this author Christian Gratzke More articles by this author Beata Rutz More articles by this author Raphaela Waidelich More articles by this author Frank Strittmatter More articles by this author Christian G. Stief More articles by this author Martin Hennenberg More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...