PD02-03 ARF1 GEF INHIBITOR GOLGICIDE A INHIBITS ADRENERGIC AND NON-ADRENERGIC PROSTATE SMOOTH MUSCLE CONTRACTION

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD02-03 ARF1 GEF INHIBITOR GOLGICIDE A INHIBITS ADRENERGIC AND NON-ADRENERGIC PROSTATE SMOOTH MUSCLE CONTRACTION Alexander Tamalunas, Amin Wendt, Ru Huang, Ruixiao Wang, Yuhan Liu, Beata Rutz, Anna Ciotkowska, Giuseppe Magistro, Christian Stief, and Martin Hennenberg Alexander TamalunasAlexander Tamalunas More articles by this author , Amin WendtAmin Wendt More articles by this author , Ru HuangRu Huang More articles by this author , Ruixiao WangRuixiao Wang More articles by this author , Yuhan LiuYuhan Liu More articles by this author , Beata RutzBeata Rutz More articles by this author , Anna CiotkowskaAnna Ciotkowska More articles by this author , Giuseppe MagistroGiuseppe Magistro More articles by this author , Christian StiefChristian Stief More articles by this author , and Martin HennenbergMartin Hennenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate smooth muscle contraction is one of the main targets for medical treatment in lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Due to an unfavorable balance between side effects and limited efficacy, current medications cause high discontinuation rates. Agonist-induced smooth muscle contractions are mediated by activation of a1-adrenoceptors, endothelin and thromboxane, and their intracellular signaling pathways including monomeric GTPases. In general, monomeric GTPases are activated by GEFs, and deactivated by GAPs. Recently, we could show, that the small monomeric GTPase ARF6 is involved in prostate smooth muscle contraction. Here, we examined the effect of the ARF1 GEF inhibitor golgicide A on agonist-induced human prostate smooth muscle contraction. METHODS: Prostate tissues were obtained from patients undergoing radical prostatectomy for prostate cancer (n=30 patients). Contractility of prostate strips was then assessed in an organ bath. Data are presented as mean ±standard deviation, with Emax and EC50 values, while group p-value is given in the diagrams. RESULTS: Noradrenaline-induced adrenergic contractions were decreased by 47±12.1% with golgicide A (10µM) for concentrations of 1-100 µM (Figure 1A), by 30±6.6% for 1-100 µM of phenylephrine-induced contractions (Figure 1B), and by 61±10.1% for 1-100 µM of methoxamine-induced contractions (Figure 1C). Additionally, golgicide A inhibited non-adrenergic contraction by thromboxane A2 analogue U46619 by 82±19.6% for 1-300 µM of U46619-induced contractions (Figure 1D), endothelin-1 induced contraction by 53±7.0% for 1-30 µM of endothelin-1-induced contractions (Figure 1E), and EFS-induced neurogenic contractions by 76±16.6% for 2-32 Hz (Figure 1F). CONCLUSIONS: Golgicide A-sensitive GEFs are involved in regulation of human prostate smooth muscle contraction, by control of ARF1 GEF activity. Knowledge about GEFs and GAPs involved in smooth muscle contraction is still limited. However, increased understanding of prostate smooth muscle contraction may assist in developing new pharmaceutical targets for LUTS medication in the future. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e69 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Tamalunas More articles by this author Amin Wendt More articles by this author Ru Huang More articles by this author Ruixiao Wang More articles by this author Yuhan Liu More articles by this author Beata Rutz More articles by this author Anna Ciotkowska More articles by this author Giuseppe Magistro More articles by this author Christian Stief More articles by this author Martin Hennenberg More articles by this author Expand All Advertisement PDF downloadLoading ...