MP31-10 ADDITIVE CONTRACTIONS BY THROMBOXANE A2 AND ENDOTHELIN-1 ARE STRONGER THAN NOREPINEPHRINE-INDUCED CONTRACTIONS IN HUMAN PROSTATE SMOOTH MUSCLE

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2015MP31-10 ADDITIVE CONTRACTIONS BY THROMBOXANE A2 AND ENDOTHELIN-1 ARE STRONGER THAN NOREPINEPHRINE-INDUCED CONTRACTIONS IN HUMAN PROSTATE SMOOTH MUSCLE Martin Hennenberg, Alice C. Acevedo, Alexander Tamalunas, Yiming Wang, Beata Rutz, Frank Strittmatter, Raphaela Waidelich, Christian G. Stief, and Christian Gratzke Martin HennenbergMartin Hennenberg More articles by this author , Alice C. AcevedoAlice C. Acevedo More articles by this author , Alexander TamalunasAlexander Tamalunas More articles by this author , Yiming WangYiming Wang More articles by this author , Beata RutzBeata Rutz More articles by this author , Frank StrittmatterFrank Strittmatter More articles by this author , Raphaela WaidelichRaphaela Waidelich More articles by this author , Christian G. StiefChristian G. Stief More articles by this author , and Christian GratzkeChristian Gratzke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1365AboutPDF 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) suggestive of benign prostate hyperplasia. Although application of α1-blockers represents the goldstandard for medical treatment, their effects are limited to max. 50%. The reasons are unknown, while only little is known about contributions of non-adrenergic mediators to prostate contraction. In vivo, different mediators probably do not occur separately, but rather act simultaneously on smooth muscle cells. Here, we compared different contractile mediators with norepinephrine, and adressed their cooperative effects in contraction of human prostate smooth muscle. METHODS Prostate tissues were obtained from radical prostatectomy (n=72 patients). Contractility of prostate strips was assessed in an organ bath. Receptor expression was detected by Western blot analysis and fluorescence staining. RESULTS Maximum endothelin-1 (ET-1)- (0.1-3 μM), endothelin-2 (ET-2)- (0.1-3 μM), and norepinephrine (NE)- (0.1-100 μM) induced contractions were of similar magnitude (ET-1 116±23% of KCl-induced contraction; ET-2 86±17%; NE 117±18%). Maximum contractions by the thromboxane analogue, U46619 (10 μM) amounted on average around 50% of NE-induced contraction (63±9% of KCl). ET-1- or ET-2-induced contractions were not affected by the α1-blocker tamsulosin (300 nM), while NE-induced contraction was virtually completely abolished and U46619-induced contraction was slightly inhibited. Dopamine (0.1-300 μM) and serotonin (0.1-300 μM) induced only very slight contractions (22±4% and 9±2% of KCl) of prostate strips, which may be of minor or local relevance. Carbachol and uridine adenosine tetraphosphate did not induce contractions. After maximum NE-induced precontraction, ET-1 did not further increase tension. In contrast, contractile effects of ET-1 (3 μM) and U46619 (10 μM) were additive, so that tension after combined application of ET-1 and U46619 (172±25% of KCl) was higher than maximum NE- (100 μM) induced tension (p<0.05). Endothelin receptor A and B were detectable by Western blot in all samples. Double fluorescence staining suggests expression in stromal smooth muscle cells. CONCLUSIONS NE-induced contraction of human prostate smooth muscle can be exceeded by cooperative actions of endothelins and thromboxane. These contractions may even occur under treatment with α1-blockers. Such contributions of non-adrenergic mediators might explain the limited efficacy of α1-blockers. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e359 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Martin Hennenberg More articles by this author Alice C. Acevedo More articles by this author Alexander Tamalunas More articles by this author Yiming Wang More articles by this author Beata Rutz More articles by this author Frank Strittmatter More articles by this author Raphaela Waidelich More articles by this author Christian G. Stief More articles by this author Christian Gratzke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...