MP44-14 INHIBITION OF ADRENERGIC AND NON-ADRENERGIC SMOOTH MUSCLE CONTRACTION IN THE HYPERPLASTIC HUMAN PROSTATE BY THE PHOSPHODIESTERASE 10-SELECTIVE INHIBITOR TC-E 5005

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2016MP44-14 INHIBITION OF ADRENERGIC AND NON-ADRENERGIC SMOOTH MUSCLE CONTRACTION IN THE HYPERPLASTIC HUMAN PROSTATE BY THE PHOSPHODIESTERASE 10-SELECTIVE INHIBITOR TC-E 5005 Martin Hennenberg, Melanie Schott, Patrick Keller, Alexander Tamalunas, Anna Ciotkowska, Beata Rutz, Raphaela Waidelich, Frank Strittmatter, Christian Stief, and Christian Gratzke Martin HennenbergMartin Hennenberg More articles by this author , Melanie SchottMelanie Schott More articles by this author , Patrick KellerPatrick Keller More articles by this author , Alexander TamalunasAlexander Tamalunas More articles by this author , Anna CiotkowskaAnna Ciotkowska 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 StiefChristian 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.2016.02.270AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The phosphodiesterase (PDE) 5 inhibitor tadalafil is available for treatment of male lower urinary tract symptoms, while the role of other PDE isoforms for prostate smooth muscle tone is still unknown. Here, we examined effects of the PDE7-selective inhibitor BRL 50481, and the PDE10-selective inhibitor TC-E 5005 on smooth muscle contraction in the hyperplastic human prostate. METHODS Prostate samples were obtained from patients (n=95) undergoing radical prostatectomy. Expression of PDE isoforms was addressed by RT-PCR, Western blot, and immunofluorescence. Effects of TC-E 5005, BRL 50481, and tadalafil on contractility of prostate strips were studied in an organ bath. RESULTS PDE7A1/2 and PDE10A were detectable by RT-PCR, Western blot, and fluorescence staining. Colocalization with calponin and tyrosine hydroxylase suggested expression of PDE7A1/2 and PDE10A in smooth muscle cells and catecholaminergic nerves. Noradrenaline, the α1-adrenergic agonist phenylephrine, the thromboxane A2 analogue U46619, and endothelins 1-3 induced concentration-dependent contractions of prostate strips, while electric field stimulation (EFS) induced frequence-dependent contractions. Application of TC-E 5005 (500 nM) caused significant inhibition of noradrenaline-, phenylephrine-, and endothelin-3-induced contractions. Similarly, TC-E 5005 caused significant inhibiton of EFS-induced contractions. Inhibition of EFS-induced contraction by TC-E 5005 amounted to approximately 50 %, resembling inhibition of EFS-induced contraction by tadalafil (10 µM) (also around 50 %) (see figure). EFS- and norepinephrine-induced tension were similar after application of tadalafil, and after combined application of tadalafil and TC-E 5005. BRL 50481 was without effect on noradrenaline-induced contraction. CONCLUSIONS The PDE10-selective inhibitor TC-E 5005 inhibits neurogenic, adrenergic, and endothelin-3-induced smooth muscle contractions in the hyperplastic human prostate. TC-E 5005 inhibits neurogenic contractions with an efficacy similar to tadalafil. Urodynamic effects in vivo appear possible. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e604 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Martin Hennenberg More articles by this author Melanie Schott More articles by this author Patrick Keller More articles by this author Alexander Tamalunas More articles by this author Anna Ciotkowska 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 Stief More articles by this author Christian Gratzke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...