MP06-14 INHIBITION OF PROSTATE SMOOTH MUSCLE CONTRACTION BY THALIDOMIDE: A NOVEL REMEDY IN LUTS?

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You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-14 INHIBITION OF PROSTATE SMOOTH MUSCLE CONTRACTION BY THALIDOMIDE: A NOVEL REMEDY IN LUTS? Alexander Tamalunas*, Cora Sauckel, Anna Ciotkowska, Christian Gratzke, Christian G. Stief, and Martin Hennenberg Alexander Tamalunas*Alexander Tamalunas* More articles by this author , Cora SauckelCora Sauckel More articles by this author , Anna CiotkowskaAnna Ciotkowska More articles by this author , Christian GratzkeChristian Gratzke 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.0000000000000820.014AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medical treatment in benign prostatic hyperplasia (BPH) includes reduction of smooth muscle tone for rapid relieve of lower urinary tract symptoms (LUTS). Current medications cause high rates of patient non-compliance due to an unfavourable balance between side effects and efficacy, with discontinuation rates peaking up to 90% for combination therapies. We have recently shown that thalidomide reduces prostate stromal cell growth and modulates cytoskeletal actin organization. Here, we addressed effects of thalidomide on adrenergic and non-adrenergic contractions of human prostate smooth muscle. METHODS: Prostate tissues were obtained from patients undergoing radical prostatectomy for prostate cancer (n=40 patients). Contractility of prostate strips was then assessed in an organ bath. RESULTS: Noradrenaline-induced adrenergic contractions were decreased up to over 56 % with thalidomide (100µM) for concentrations of 1-100 µM (p<0.05, p<0.03, p<0.02, p<0.01, p<0.02 for 1 µM, 3 µM, 10 µM, 30 µM and 100 µM noradrenaline, respectively, for thalidomide vs. control, fig. A). Thalidomide caused significant inhibition of up to 90 % at 1-100 µM for both methoxamine- and phenylephrine-induced contractions (p<0.04, p<0.03, p<0.04, p<0.04, p<0.03 and p<0.05, p<0.02, p<0.03, p<0.02, p<0.01 for 1 µM, 3 µM, 10 µM, 30 µM and 100 µM phenylephrine and methoxamine, respectively, for thalidomide vs. control, fig. B & C). Thalidomide inhibited non-adrenergic contraction with thromboxane A2 analogue U46619 at 0.1 µM, 0.3 µM, 3 µM, 10 µM and 30 µM (p<0.01 for 0.1 µM, 0.3 µM, 10 µM and 30 µM and p<0.02 for 3 µM U46619, respectively, for thalidomide vs. control) and up to 58 % of endothelin-1-induced contractions at 0.3 µM, 1 µM and 3 µM (p<0.02, p<0.03 and p<0.03 for 0.3 µM, 1 µM and 3 µM endothelin-1, respectively, for thalidomide vs. control, fig. D & E). Significant inhibition up to 73 % also occurred in EFS-induced neurogenic contractions for 2-32 Hz (p<0.01, p<0.05, p<0.04, p<0.03, p<0.03 for 2, 4, 8, 16 and 32 Hz, respectively, for thalidomide vs. control, fig. F). CONCLUSIONS: Thalidomide not only inhibits prostate stromal cell growth and modulates cytoskeletal development, but also inhibits adrenergic and non-adrenergic prostate smooth muscle contraction. Therefore, thalidomide may be superior to current medical treatment. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e56-e56 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Tamalunas* More articles by this author Cora Sauckel More articles by this author Anna Ciotkowska More articles by this author Christian Gratzke More articles by this author Christian G. Stief More articles by this author Martin Hennenberg More articles by this author Expand All Advertisement PDF downloadLoading ...