798 SPINAL EFFECTS OF GLYCINE TRANSPORTER-1 INHIBITOR ON THE MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research1 Apr 2011798 SPINAL EFFECTS OF GLYCINE TRANSPORTER-1 INHIBITOR ON THE MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS Mayuko Matsumoto, Masashi Honda, Seiya Inoue, Nobuyuki Hinata, and Atsushi Takenaka Mayuko MatsumotoMayuko Matsumoto Yonago, Japan More articles by this author , Masashi HondaMasashi Honda Yonago, Japan More articles by this author , Seiya InoueSeiya Inoue Yonago, Japan More articles by this author , Nobuyuki HinataNobuyuki Hinata Yonago, Japan More articles by this author , and Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.616AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Glycine is an important inhibitory neurotransmitter in the central nervous system, including neural pathways controlling the lower urinary tract. Two types of glycine transporters (GlyTs) such as GlyT-1 and GlyT-2 have been cloned so far. In the current study we tested whether a selective GlyT-1 inhibitor that can increase endogenous glycine concentration affects the micturition reflex in urethane anesthetized rats. METHODS Female Sprague-Dawley rats (232–265 g) were used. Continuous cystometrograms (CMG, 0.04 ml/min) were performed in two groups of urethane-anesthetized rats. A group of 24 rats was used for intrathecal administration of 1–30 μg of ALX5407, a selective GlyT-1 inhibitor, via an intrathecal catheter. In the second group of 24 rats, 1–30 μg of ALX5407 were administered intracerebroventricularly via a catheter inserted into the lateral ventricle. Micturition parameters were recorded and compared before and after drug administration. RESULTS Intrathecal administration of ALX5407 at 1, 3, 10 and 30 μg increased intercontraction intervals at doses of 3 μg or higher in a dose-dependent fashion to 101.8 ± 5.7%, 122.1 ± 7.6%, 135.7 ± 7.8% and 156.9 ± 16.7% of the control value, respectively (at 3, 10 and 30 μg, p<0.01). These inhibitory effects were observed immediately after administration. Intrathecal administration of ALX5407 at 1, 3, 10 and 30 μg also increased pressure threshold at doses of 3 μg or higher in a dose-dependent fashion to 8.14 ± 0.77 cmH2O, 9.98 ± 0.79 cmH2O, 13.47 ± 0.91 cmH2O and 16.93 ± 1.83 cmH2O, respectively (at 3, 10 and 30 μg, p<0.01). However, when ALX5407 (1, 3, 10 and 30 μg, n=6 per dose) were administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure, baseline pressure or residual urine at any doses tested. CONCLUSIONS The results of this study show that, in urethane-anesthetized rats, suppression of GlyT-1 by ALX5407 has an inhibitory effect on the micturition reflex at the spinal level. Thus, GlyT-1 inhibitors could be effective for the treatment of bladder dysfunction such as overactive bladder. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e321 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mayuko Matsumoto Yonago, Japan More articles by this author Masashi Honda Yonago, Japan More articles by this author Seiya Inoue Yonago, Japan More articles by this author Nobuyuki Hinata Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...