1684 EFFECT OF ADENOSINE A 2A RECEPTOR ANTAGONIST ON BLADDER OVERACTIVITY IN RATS WITH CHEMICAL CYSTITIS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-Neurogenic Voiding Dysfunction II1 Apr 20101684 EFFECT OF ADENOSINE A2A RECEPTOR ANTAGONIST ON BLADDER OVERACTIVITY IN RATS WITH CHEMICAL CYSTITIS Takeya Kitta, Katsuya Nonomura, and Naoki Yoshimura Takeya KittaTakeya Kitta Pittsburgh, PA More articles by this author , Katsuya NonomuraKatsuya Nonomura Hokkaido, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1509AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adenosine is an endogenous neurotransmitter that exerts numerous physiological effects in many organs. Moreover, there is increasing evidence showing therapeutic potentials of adenosine receptor modulation in various disease conditions such as pain. In this study, we examined the effect of adenosine A2A receptor antagonists on bladder activity in normal and cystitis rats. METHODS Female Sprague-Dawley rats were used. Continuous cystometrograms during saline or 0.2% acetic acid (AA) infusion (0.04ml/min) were recorded under urethane anesthesia. After a stabilization period, ZM24138 (ZM, adenosine A2A receptor antagonist) was administered intravenously (iv, 1 mg/kg), intrathecally (it, 10 μg), intracerebroventricularly (icv, 10 μg) or intravesically (after urothelial permeability was increased by DMSO retained in the bladder for 30 min). Micturition parameters (intercontraction interval [ICI] and maximum voiding pressure [MVP]) were recorded and compared pre and post-drug administration. RESULTS In comparison to saline infusion, AA significantly reduced ICI by 67.8%. Intravesical administration of ZM did not change any parameters. However, iv, it or icv administration of ZM significantly increased ICI in both saline and AA infusion groups while no change was detected in MVP. Moreover, during AA infusion, the inhibitory effects induced by iv and it ZM administration were significantly greater than those during saline infusion (post-ZM ICI increase: 103.1±25.2 vs. 26.6±10.0% and 203.4±40.9 vs. 98.5±26.4%, respectively) (Figure). CONCLUSIONS During saline or AA infusion, the A2A antagonist increased ICI without affecting MVP, suggesting an action on bladder afferent rather than efferent pathways. Because the inhibitory effect of iv or it A2A antagonist was enhanced after AA infusion, which induces bladder overactivity mainly due to C-fiber bladder afferent activation, the A2A receptor mediated adenosinergic mechanism in the spinal cord might be enhanced following C-fiber afferent stimulation. Thus adenosine A2A antagonists could be effective for the treatment of overactive bladder and/or bladder hypersensitive disorders such as BPS/IC. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e651 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takeya Kitta Pittsburgh, PA More articles by this author Katsuya Nonomura Hokkaido, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...