MP21-20 INTRAVESICAL INHIBITION OF P2X3 RECEPTORS IMPROVES BLADDER DYSFUNCTION DEPENDING ON UROTHELIAL EXPRESSION LEVELS FOR THE RECEPTOR IN SCI RATS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology II1 Apr 2015MP21-20 INTRAVESICAL INHIBITION OF P2X3 RECEPTORS IMPROVES BLADDER DYSFUNCTION DEPENDING ON UROTHELIAL EXPRESSION LEVELS FOR THE RECEPTOR IN SCI RATS Jorge Tovar-Perez, Broderick Sutton, Timothy Boone, and Alvaro Munoz Jorge Tovar-PerezJorge Tovar-Perez More articles by this author , Broderick SuttonBroderick Sutton More articles by this author , Timothy BooneTimothy Boone More articles by this author , and Alvaro MunozAlvaro Munoz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.972AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES P2X3-purinergic receptors (P2X3R) are expressed in afferent nerve terminals of the urinary bladder where ATP released from the urothelium during filling increase nerve activity to begin the micturition reflex. P2X3R are also expressed in the urothelium, however, its physiological role is less clear. Our objectives were 1) to determine the cystometric effects of AF-353, a specific P2X3R antagonist, in intact animals and spinal cord injured (SCI) rats with neurogenic bladder; and 2) to compare the differences on urothelial P2X3R expression between groups. METHODS Neurogenic bladder conditions were induced in female Sprague-Dawley rats via a partial bilateral-transection of the dorsal spinal cord at the Th8/Th9 region. Intact rats were used as controls. At 2 (SCI2W) or 4 weeks (SCI4W) post-SCI, rats were anesthetized with urethane and implanted with a suprapubic catheter for cystometry. Saline infusion was started at a rate of 0.1 ml/min. After baseline recordings (60–90 minutes), infusion containing AF-353 (10 μM) was initiated for a similar period of time. Thereafter, rats were perfused with iced-cold paraformaldehyde (4%). The bladder was isolated for immunostaining with a P2X3R antibody (abcam; 1:1,000) and DAPI. Confocal images were obtained at 40X. The bladder peak pressure (BPP), intercontractile intervals (ICI), and the frequency of voiding (VC) and non-voiding (NVC) contractions were determined. Changes were normalized with the respect to the saline-infusion values. RESULTS Inhibition of P2X3R had minor effects on increasing the ICI in SCI2W rats, but significantly increased the ICI value in control and SCI4W rats. Application of AF-353 also decreased the frequency of NVC in both the SCI2W and SCI4W animals. The qualitative evaluation using confocal microscopy suggests that in comparison with the control bladders, the expression of P2X3R is reduced in SCI2W but increased in SCI4W rats. CONCLUSIONS Our results suggest that the reduced effect of AF-353 to increased ICI in SCI2W rats may be related to a reduced expression of urothelial P2X3R. It is also reasonable to suggest that urothelial P2X3R may play a role in regulating ICI and the frequency of NVC in SCI rats. Pharmacological inhibition of P2X3R to treat neurogenic bladder conditions may be a beneficial therapy but requires taking into consideration the duration of the dysfunction. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e240 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jorge Tovar-Perez More articles by this author Broderick Sutton More articles by this author Timothy Boone More articles by this author Alvaro Munoz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...