Mp82-16 bladder smooth muscle contractility is inhibited by hc030031 independently of trpa1

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2017MP82-16 BLADDER SMOOTH MUSCLE CONTRACTILITY IS INHIBITED BY HC030031 INDEPENDENTLY OF TRPA1 Karel Dewulf, Jan Franken, Pieter Uvin, Yves Deruyver, Wouter Everaerts, Dirk De Ridder, and Thomas Voets Karel DewulfKarel Dewulf More articles by this author , Jan FrankenJan Franken More articles by this author , Pieter UvinPieter Uvin More articles by this author , Yves DeruyverYves Deruyver More articles by this author , Wouter EveraertsWouter Everaerts More articles by this author , Dirk De RidderDirk De Ridder More articles by this author , and Thomas VoetsThomas Voets More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2563AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES TRPA1, a member of the Transient Receptor Potential (TRP) ion channel superfamily, is expressed in sensory afferents innervating the bladder, and activation of this channel induces urinary frequency in mice and rats. To investigate the role of TRPA1 in bladder physiology, researchers have often used HC030031 as a selective TRPA1 antagonist. In organ bath studies, concentrations between 1 and 100 μM are typically used. Preliminary data from our lab indicated inhibition of detrusor contractility with HC03031 (100 μM) in TRPA1 knock out mice.Our aim is to evaluate if HC030031 (100 μM) inhibits detrusor contractility in a TRPA1-independent manner. METHODS The effect of HC030031 on detrusor contractility was examined in an organ bath study in wild type (WT) and TRPA1 knock-out (KO) C57Bl/6 mice. Contractile forces to cold (10°C), KCl (120 mM), carbachol (10 μM) and electrical field stimulation (EFS: 50V, 20Hz, 0,5ms, 10s) were recorded before, and after addition of HC030031 (100 μM), and following wash out. Contractile responses are reported as percentage of the first stimulus with the respective agonist. Statistical analyses were performed using Mann-Whitney U test and Kruskal-Wallis test. RESULTS In WT animals, HC030031 (100 μM) partially inhibited all tested agonist-induced detrusor contractions. We observed a 46 ± 5 % reduction of the contractile response to KCl, a 45 ± 4 % reduction to carbachol and a 32 ± 6 % reduction to EFS. Importantly, similar blocking potency was observed in TRPA1 KO-animals, where HC030031 (100 μM) inhibited the contractile response to KCl by 59 ± 5 % and to carbachol by 61 ± 4 %. CONCLUSIONS HC030031 (100 μM) inhibits detrusor contractility independent of TRPA1. Further research is necessary to investigate the target of HC030031. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1103 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Karel Dewulf More articles by this author Jan Franken More articles by this author Pieter Uvin More articles by this author Yves Deruyver More articles by this author Wouter Everaerts More articles by this author Dirk De Ridder More articles by this author Thomas Voets More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...