253 INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTOR MGLU5 IN PUDENDAL INHIBITION OF BLADDER OVERACTIVITY IN CATS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2012253 INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTOR MGLU5 IN PUDENDAL INHIBITION OF BLADDER OVERACTIVITY IN CATS Jeffrey Larson, P. Dafe Ogagan, Jicheng Wang, Bing Shen, James Roppolo, Changfeng Tai, and William C. de Groat Jeffrey LarsonJeffrey Larson Pittsburgh, PA More articles by this author , P. Dafe OgaganP. Dafe Ogagan Pittsburgh, PA More articles by this author , Jicheng WangJicheng Wang Pittsburgh, PA More articles by this author , Bing ShenBing Shen Pittsburgh, PA More articles by this author , James RoppoloJames Roppolo Pittsburgh, PA More articles by this author , Changfeng TaiChangfeng Tai Pittsburgh, PA More articles by this author , and William C. de GroatWilliam C. de Groat Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.310AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neuromodulation is a useful treatment modality in patients with refractory lower urinary tract symptoms, but the mechanisms of action are poorly understood. Metabotropic glutamate receptors are implicated in neuropathic pain syndromes but their involvement in micturition is poorly understood. We hypothesized that pudendal inhibition of bladder overactivity could be due to activation of the mGlu5 receptor. We used a selective mGluR5 antagonist (MTEP) to assess this receptor's function during neuromodulation. METHODS MTEP was administered to 11 cats in increasing cumulative doses. Saline (n=5) or 0.25% acetic acid (n=6) were utilized to irritate the bladder and induce overactivity. Bladder capacity and the degree of inhibition of bladder activity induced by pudendal nerve stimulation were assessed by cystometrogram. RESULTS In the absence of pudendal nerve stimulation, MTEP significantly increased saline bladder capacity. Infusion of acetic acid (AA) significantly reduced bladder capacity compared to saline. During saline CMGs, pudendal nerve stimulation significantly inhibited bladder contraction and increased bladder capacity by 196 ±37.4%; a smaller increase in bladder capacity was observed with AA infusion (98.4 ± 55.2%). Administration of MTEP doses of ≥ 1mg/kg significantly blocked the pudendal nerve inhibition of bladder contractions during AA infusion. At all doses tested during saline infusion, MTEP significantly increased baseline bladder capacity without neuromodulation. CONCLUSIONS MTEP can suppress reflex micturition as well as pudendal nerve stimulation induced inhibition of bladder activity. These results indicate that glutamic acid is an excitatory transmitter in the micturition pathway essential to the pudendal nerve stimulation evoked inhibitory mechanism. The mGlu5 receptor could serve as a novel and important potential new target for the treatment of OAB. Potential mGluR5 locations include spinal cord inhibitory interneurons, spinal tract neurons, or upper tract CNS. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e102-e103 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Larson Pittsburgh, PA More articles by this author P. Dafe Ogagan Pittsburgh, PA More articles by this author Jicheng Wang Pittsburgh, PA More articles by this author Bing Shen Pittsburgh, PA More articles by this author James Roppolo Pittsburgh, PA More articles by this author Changfeng Tai Pittsburgh, PA More articles by this author William C. de Groat Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...