MP17-07 INTRAVESICAL ADMINISTRATION OF SENSORY NEURON-SPECIFIC RECEPTOR AGONIST INHIBITS THE MICTURITION REFLEX OF ANESTHETIZED RATS (2014)

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology1 Apr 2014MP17-07 INTRAVESICAL ADMINISTRATION OF SENSORY NEURON-SPECIFIC RECEPTOR AGONIST INHIBITS THE MICTURITION REFLEX OF ANESTHETIZED RATS Masashi Honda, Shinji Hirano, Bunya Kawamoto, Shogo Shimizu, Naoto Kobayashi, Katsuya Hikita, Kuniyasu Muraoka, Motoaki Saito, Takehiro Sejima, Atsushi Takenaka, Michael Chancellor, and Naoki Yoshimura Masashi HondaMasashi Honda More articles by this author , Shinji HiranoShinji Hirano More articles by this author , Bunya KawamotoBunya Kawamoto More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Naoto KobayashiNaoto Kobayashi More articles by this author , Katsuya HikitaKatsuya Hikita More articles by this author , Kuniyasu MuraokaKuniyasu Muraoka More articles by this author , Motoaki SaitoMotoaki Saito More articles by this author , Takehiro SejimaTakehiro Sejima More articles by this author , Atsushi TakenakaAtsushi Takenaka More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.528AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A novel family of G-protein-coupled receptors has been identified in rat dorsal root ganglia and named as sensory neuron-specific receptors (SNSRs). Recent studies have demonstrated that intrathecal or intravenous administration of a SNSR1 agonist can inhibit the micturition reflex. However, it is unknown whether SNSR1 receptor activation in the bladder can locally affect the micturition reflex. In the current study we tested whether intravesical administration of bovine adrenal medulla 8-22 (BAM 8-22), a selective rat SNSR1 agonist, can affect the micturition reflex in urethane-anesthetized rats. METHODS Twelve-week-old female Sprague-Dawley rats (238-250 g) were used. Continuous cystometrograms (CMG, 0.04ml/min) were performed in urethane-anesthetized rats. After stable micturition cycles were established, vehicle (saline) or BAM 8-22 was instilled intravesically and changes in bladder activity were monitored. The experiments using BAM 8-22 were also performed in rats pretreated with systemic capsaicin 4 days before the experiments to determine whether the effect of BAM 8-22 was mediated by capsaicin sensitive C-fiber afferent pathways. Micturition parameters were recorded and compared before and after drug administration. RESULTS Intravesical administration of BAM 8-22 at 100, 300 and 1000 nM in 8 preparations per dose significantly increased intercontraction intervals at doses of 300 nM or higher in dose dependent fashion to 101.2 ± 4.8%, 115.5 ± 8.7% and 119.4 ± 10.5% of the control value, respectively (p<0.01 at 300 and 1000 nM). Intravesical administration of BAM 8-22 at 100, 300 and 1000 nM also increased pressure thresholds at doses of 300 nM or higher in dose dependent fashion to 5.83 ± 1.35 cmH2O, 8.85 ± 2.16 cmH2O and 8.96 ± 2.74 cmH2O, respectively, from the control value of 5.28 ± 1.61 cmH2O (p<0.01 at 300 and 1000 nM), but did not affect baseline pressure or maximum voiding pressure at any doses tested. The inhibitory effects of intravesical administration of BAM 8-22 (1000 nM, n=8) were not inhibited by capsaicin pretreatment. CONCLUSIONS These results indicate that intravesical administration of a SNSR1 agonist can inhibit the micturition reflex via suppression of afferent pathways independent of capsaicin-sensitive C-fibers in rats. Thus, SNSRs could be an effective target for treating bladder dysfunction such as overactive bladder. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e137 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Masashi Honda More articles by this author Shinji Hirano More articles by this author Bunya Kawamoto More articles by this author Shogo Shimizu More articles by this author Naoto Kobayashi More articles by this author Katsuya Hikita More articles by this author Kuniyasu Muraoka More articles by this author Motoaki Saito More articles by this author Takehiro Sejima More articles by this author Atsushi Takenaka More articles by this author Michael Chancellor More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...