273 INVOLVEMENT OF 5-HT2 RECEPTOR IN PUDENDAL NERVE INHIBITION OF NOCICEPTIVE AND NON-NOCICEPTIVE BLADDER ACTIVITY IN CATS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology (I)1 Apr 2013273 INVOLVEMENT OF 5-HT2 RECEPTOR IN PUDENDAL NERVE INHIBITION OF NOCICEPTIVE AND NON-NOCICEPTIVE BLADDER ACTIVITY IN CATS Yosuke Matsuta, Zeyad Schwen, Abhijith Mally, Bing Shen, Jicheng Wang, James Roppolo, William de Groat, and Changfeng Tai Yosuke MatsutaYosuke Matsuta Pittsburgh, PA More articles by this author , Zeyad SchwenZeyad Schwen Pittsburgh, PA More articles by this author , Abhijith MallyAbhijith Mally Pittsburgh, PA More articles by this author , Bing ShenBing Shen Pittsburgh, PA More articles by this author , Jicheng WangJicheng Wang Pittsburgh, PA More articles by this author , James RoppoloJames Roppolo Pittsburgh, PA More articles by this author , William de GroatWilliam de Groat Pittsburgh, PA More articles by this author , and Changfeng TaiChangfeng Tai Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1657AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Understanding the neurotransmitter mechanisms involved in pudendal nerve inhibition of bladder activity could lead to identify new pharmacological targets for overactive bladder (OAB). Currently little is known about the effect of 5-hydroxytryptamine (5-HT)2 receptor on micturition reflex. This study used methysergide, a 5-HT2 receptor antagonist, and naloxone, an opioid receptor antagonist, to examine the involvement of these receptors in the inhibition of micturition reflex induced by pudendal nerve stimulation (PNS). METHODS Experiments were conducted in 20 cats under α-chloralose anesthesia. A tripolar cuff electrode was applied around the right pudendal nerve and connected to a stimulator. Drugs were administered via the right cephalic vein. Pharmacological studies were performed in two experimental groups (i.e. AA and saline group). In both group, cumulative doses (0.01, 0.03, 0.1, 0.3, and 1 mg/kg) of methysergide and then naloxone (1 mg/kg) were given. RESULTS AA irritated the bladder, induced bladder overactivity and significantly (p < 0.0001) reduced bladder capacity (BC) to 27.0 ± 7.4 % of saline control capacity. PNS (5 Hz, 0.2 ms) at 1-2 and 3-4 times the threshold (T) intensity for inducing an observable twitching of anal sphincter suppressed AA-induced bladder overactivity and significantly increased BC to 60.1 ± 8.0 % at 1-2T (p < 0.0001) and 92.2 ± 14.1 % at 3-4T (p = 0.001) of the saline control capacity. Methysergide (0.03-1 mg/kg, i.v.) suppressed PNS inhibition of bladder overactivity at low intensity (1-2T) but not at high intensity (3-4T). During saline infusion PNS increased BC to 150.8 ± 9.9 % at 1-2T (p < 0.01) and 180.4 ± 16.6 % at 3-4T (p < 0.01) of the saline control capacity. Methysergide significantly increased BC at the doses of 0.1-1 mg/kg (p < 0.05) and suppressed pudendal inhibition. After 1 mg/kg dose of methysergide, naloxone significantly (p < 0.05) reduced BC in AA condition, however, PNS-induced inhibition at 3-4T was still observed. On the other hand, naloxone did not change BC and PNS-induced inhibition in saline condition. CONCLUSIONS These results suggest that 5-HT2 receptor antagonist plays an inhibitory role in both nociceptive and non-nociceptive bladder activity. 5-HT2 receptor interacts with opioid receptor in micturition reflex pathway. Our study indicates methysergide (a FDA-approved drug with few side effects) could be a new treatment for OAB. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e111 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yosuke Matsuta Pittsburgh, PA More articles by this author Zeyad Schwen Pittsburgh, PA More articles by this author Abhijith Mally Pittsburgh, PA More articles by this author Bing Shen Pittsburgh, PA More articles by this author Jicheng Wang Pittsburgh, PA More articles by this author James Roppolo Pittsburgh, PA More articles by this author William de Groat Pittsburgh, PA More articles by this author Changfeng Tai Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...