MP12-19 SPONTANEOUS MICTURITION BEHAVIOR AND CYSTOMETRIC EVALUATION OF BLADDER FUNCTION IN P2X7 RECEPTOR DEFICIENT MICE

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research II1 Apr 2015MP12-19 SPONTANEOUS MICTURITION BEHAVIOR AND CYSTOMETRIC EVALUATION OF BLADDER FUNCTION IN P2X7 RECEPTOR DEFICIENT MICE Hiromitsu Negoro, Nuan Cui, Osamu Ogawa, and Sylvia Suadicani Hiromitsu NegoroHiromitsu Negoro More articles by this author , Nuan CuiNuan Cui More articles by this author , Osamu OgawaOsamu Ogawa More articles by this author , and Sylvia SuadicaniSylvia Suadicani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.794AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES ATP signaling plays major roles in the bladder sensory and motor functions. Several P2 receptor (P2R) subtypes are expressed in the bladder but little is till known of their actual individual role in bladder function and dysfunction. Studies have indicated a role for P2X7R in hemorrhagic cystitis, and recently the P2X7R participation in urothelial mechanosensory transduction. We have investigated the extent to which deletion of P2X7R affects bladder function. METHODS Three months old female wild-type and P2X7R-null mice were used. Expression of P2X7R was assessed by immunoblotting. Spontaneous micturition behavior was assessed using the automated voided stain on paper (aVSOP) method. Cystometric parameters measured: Bladder capacity (BC, µL), micturition volume (MV, µL), residual volume (RV; µL), bladder compliance (BCo, μL/cmH2O), basal pressure (BP; cmH2O), threshold pressure (TP; cmH2O) and micturition pressure (MP; cmH2O). Effects of P2X7R deletion on bladder function was also evaluated as changes in intravesical stretch-induced ATP release. RESULTS P2X7R expression in mucosa and detrusor was confirmed in WT and no expression in P2X7R-null mice. Body weight and gross bladder morphology did not differ between WT and P2X7R-null. ATP release was 60% lower in P2X7R-null compared to WT (WT: 0.9±0.2nM vs P2X7R: 0.3±0.03nM; N=9 and 7, P<0.05). aVSOP analysis demonstrated that voided volume per micturition was significantly higher in P2X7R-null than in WT but frequency and total urine volume were not (average of 4 hours, N=3 and 5, P<0.05, shown in figure). Cystometric analysis indicated that P2X7R-null mice display higher BC (WT: 127.1±4.7; P2X7R: 187.9±3.3; N=6 and 6, P<0.0001), MV (WT: 81.0±4.6; P2X7R: 142.0±4.3, P<0.0001), MP (WT: 25.4±0.6, P2X7R: 31.3±0.8, P<0.0001), TP (WT: 18.3±0.5, P2X7R: 21.5±0.8; P<0.01) and BCo (WT: 16.3±2.2; P2X7R: 70.7±12.7, P<0.001). BP was lower in P2X7R-null compared to WT mice (WT: 7.9±0.2; P2X7R: 6.0±0.2, P<0.0001). RV was similar (WT: 45.9±3.2; P2X7R: 44.1±3.5). CONCLUSIONS P2X7R deficient mice display significant changes in bladder function. These changes likely result from decreased urothelial ATP release and signaling, and consequent reduced sensory activation in response to bladder distension. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e135 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiromitsu Negoro More articles by this author Nuan Cui More articles by this author Osamu Ogawa More articles by this author Sylvia Suadicani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...