PD11-07 MIRABEGRON INHIBITS NEUROGENIC AND α 1 -ADRENERGIC HUMAN PROSTATE SMOOTH MUSCLE CONTRACTIONS, WITH SIMILAR PHARMACOLOGIC PATTERNS AS α 1 -BLOCKERS

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-07 MIRABEGRON INHIBITS NEUROGENIC AND α1-ADRENERGIC HUMAN PROSTATE SMOOTH MUSCLE CONTRACTIONS, WITH SIMILAR PHARMACOLOGIC PATTERNS AS α1-BLOCKERS Ru Huang, Yuhan Liu, Bingsheng Li, Ruixiao Wang, Alexander Tamalunas, Raphaela Waidelich, Frank Strittmatter, Christian G. Stief, and Martin Hennenberg Ru HuangRu Huang More articles by this author , Yuhan LiuYuhan Liu More articles by this author , Bingsheng LiBingsheng Li More articles by this author , Ruixiao WangRuixiao Wang More articles by this author , Alexander TamalunasAlexander Tamalunas 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/10.1097/JU.0000000000001986.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mirabegron inhibits detrusor smooth muscle contractions and is available for treatment of overactive bladder. Consequently, its effects on lower urinary tract symptoms (LUTS) suggestive of bengin prostatic hyperplasia (BPH) were subject of recent trials. However, available results are not yet conclusive, and effects of mirabegron on human prostate smooth muscle contraction are hardly characterized. Voiding symptoms suggestive of BPH may be driven by increased prostate smooth muscle tone. Here, we examined effects of mirabegron on contractions of human prostate tissues. METHODS: Human prostate tissues were obtained from radical prostatectomy. Contractions were studied in an organ bath. Comparisons were performed between whole groups (one-way ANOVA), and at single frequencies and agonist concentrations (multivariate analysis). RESULTS: Electric field stimulation (EFS) induced neurogenic, frequence-dependent contractions, while agonists induced concentration-dependent contractions. Mirabegron (10 µM) inhibited EFS-induced contractions (p <0.001 for controls vs. mirabegron between whole groups), which was observed at different frequencies and reflected by reduced Emax values calculated by curve fitting (contractions in controls 84±11% of KCl-induced contractions, but 14±2% after mirabegron, p <0.01). Miragebron increased the EC50 values for noradrenaline (controls 0.55±0.32 µM, mirabegron 5.1±2.4 µM, p <0.004), resulting in rightshifts of concentration response curves for noradrenaline-induced contractions (p <0.001) and in reduced contractions up to 10 µM noradrenaline, but in recovery at higher noradrenaline concentrations and unchanged Emax values. Similarly, EC50 values for the α1-adrenergic agonist phenylephrine were increased by mirabegron (controls 7.4±4.1 µM, mirabegron 29.2±8.9 µM, p=0.05), resulting in rightshifts of concentration response curves for phenylephrine (p <0.001) and in reduced contractions up to 30 µM phenylephrine, but in recovery at higher phenylephrine concentrations and in unchanged Emax values. Mirabegron slightly reduced contractions induced by the thromboxane A2 analog U46619 (p <0.03), without changing EC50 values. Contractions induced by endothelin-1 remained unchanged by mirabegron. CONCLUSIONS: Mirabegron inhibits neurogenic and α1-adrenergic smooth muscle contractions in the human prostate. Surprisingly, the pharmacologic pattern is similar to that of α1-blockers, including rightshifts of α1-adrenergic concentration response curves, reduced Emax values for neurogenic contractions, and lacking or small effects on non-adrenergic contractions. Source of Funding: China Scholarship Council (CSC) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e200-e200 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ru Huang More articles by this author Yuhan Liu More articles by this author Bingsheng Li More articles by this author Ruixiao Wang More articles by this author Alexander Tamalunas 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 Loading ...