31 THE ROLE OF TRPA1 IN THE BLADDER COOLING REFLEX; A POSSIBLE NEW THERAPEUTIC TARGET

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You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (1)1 Apr 201331 THE ROLE OF TRPA1 IN THE BLADDER COOLING REFLEX; A POSSIBLE NEW THERAPEUTIC TARGET Pieter Uvin, Mathieu Boudes, Jan Franken, Silvia Pinto, Wouter Everaerts, Anne-Cathérine Boeve, Roma Rietjens, Yeranddy A. Alpizar, Grzegorz Owsianik, Karel Talavera, Dirk De Ridder, and Thomas Voets Pieter UvinPieter Uvin Leuven, Belgium More articles by this author , Mathieu BoudesMathieu Boudes Leuven, Belgium More articles by this author , Jan FrankenJan Franken Leuven, Belgium More articles by this author , Silvia PintoSilvia Pinto Leuven, Belgium More articles by this author , Wouter EveraertsWouter Everaerts Leuven, Belgium More articles by this author , Anne-Cathérine BoeveAnne-Cathérine Boeve Leuven, Belgium More articles by this author , Roma RietjensRoma Rietjens Leuven, Belgium More articles by this author , Yeranddy A. AlpizarYeranddy A. Alpizar Leuven, Belgium More articles by this author , Grzegorz OwsianikGrzegorz Owsianik Leuven, Belgium More articles by this author , Karel TalaveraKarel Talavera Leuven, Belgium More articles by this author , Dirk De RidderDirk De Ridder Leuven, Belgium More articles by this author , and Thomas VoetsThomas Voets Leuven, Belgium More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1406AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For decades, bladder contraction upon instillation of ice-cold saline into the bladder has been used as a diagnostic test for neurogenic detrusor overactivity (NDO). TRPA1 is a member of the Transient Receptor Potential (TRP) ion channel superfamily that is activated by irritant chemicals, as well as cold temperatures. TRPA1 is expressed in sensory afferents in the bladder and chemical activation of this channel induces urinary frequency in mice and rats. We hypothesized that TRPA1 plays a crucial role in the bladder cooling reflex, leading to ice-water induced detrusor overactivity. METHODS Female 10-12 weeks old Wistar rats were used for experiments. Expression of TRPA1 was assessed by quantitative RT-PCR on L6-S1 dorsal root ganglion neurons (DRG), urothelial cells and detrusor smooth muscle cells. Functional responses to cold stimuli were evaluated in ex vivo isolated detrusor strip contractility measurements. In vivo cystometry recordings were performed in urethane-anaesthetized rats (1g/kg, intraperitoneal (i.p.) injection) and in conscious rats 3-4 weeks after spinal cord injury (SCI). The TRPA1 blocker HC030031 (100mg/kg, i.p.), the ganglionic blocker hexamethonium (20mg/kg, i.p.) and the vehicle were administered 20 minutes before the cold stimulus. RESULTS TRPA1 is highly expressed in DRG neurons, while the expression in urothelium and detrusor is very low (n = 3). In urethane-anaesthetized (n = 8) and SCI rats (n = 7), the intravesical pressure increases were observed upon instillation of ice-cold saline. These effects were significantly smaller in HC030031 pretreated animals, compared to vehicle. Administration of hexamethonium had no effect on the bladder cooling reflex (n = 6). In detrusor strip experiments, we observed a clear cold-induced contraction (n = 8), which could be largely abolished by the TRPA1 blocker HC030031 (100μM) (n = 8). This cold-induced bladder contraction was significantly diminished in a 0 Ca2+ BAPTA solution (n = 8) and in indomethacin 1μM (n = 8) but not in atropine 1μM (n = 8) and suramine 300μM (n = 8). CONCLUSIONS The bladder cooling reflex in rats is largely mediated by TRPA1. Surprisingly, it doesn't involve a spinar reflex arch, but seems to be a “local” phenomenon via local release of neuropeptides. Ultimately, TRPA1 could become an important therapeutic target to relieve symptoms in patients with NDO and OAB. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e12 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pieter Uvin Leuven, Belgium More articles by this author Mathieu Boudes Leuven, Belgium More articles by this author Jan Franken Leuven, Belgium More articles by this author Silvia Pinto Leuven, Belgium More articles by this author Wouter Everaerts Leuven, Belgium More articles by this author Anne-Cathérine Boeve Leuven, Belgium More articles by this author Roma Rietjens Leuven, Belgium More articles by this author Yeranddy A. Alpizar Leuven, Belgium More articles by this author Grzegorz Owsianik Leuven, Belgium More articles by this author Karel Talavera Leuven, Belgium More articles by this author Dirk De Ridder Leuven, Belgium More articles by this author Thomas Voets Leuven, Belgium More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...