496 THE ROLE OF SOMATOSTATIN RECEPTOR SUBTYPE-4 IN MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS (2012)

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology II1 Apr 2012496 THE ROLE OF SOMATOSTATIN RECEPTOR SUBTYPE-4 IN MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS Masashi Honda, Seiya Inoue, Nobuyuki Hinata, Tadahiro Isoyama, Takehiro Sejima, Atsushi Takenaka, Michael Chancellor, and Naoki Yoshimura 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 , Tadahiro IsoyamaTadahiro Isoyama Yonago, Japan More articles by this author , Takehiro SejimaTakehiro Sejima Yonago, Japan More articles by this author , Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author , Michael ChancellorMichael Chancellor Royal Oak, MI 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.2012.02.566AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Somatostatin binds to G-protein-coupled membrane receptors (sst1-sst5). Recent studies have demonstrated that somatostatin has an important role in neuromodulations such as pain control, presumably via somatostatin subtype-4 (sst4) receptor. However, it is not known whether sst4 receptor has a role in the control of the micturition reflex. The therapeutic value of native somatostatin is limited by its broad range of effects, mediated by five different receptor subtypes and its short plasma half life. However, potent and stable somatostatin receptor agonists acting selectively on sst4 receptor have been synthesized and investigated. Therefore, we examined the effects of activation of sst4 receptor on the micturition reflex in rats. METHODS Continuous cystometrograms (CMG, 0.04ml/min infusion rate) were performed in female Sprague-Dawley rats (242-265 g) under urethane anesthesia. After stable micturition cycles were established, a selective sst4 receptor agonist, NNC 26-9100, was administered intravenously in normal rats or rats pretreated with capsaicin 4 days before the experiments. Micturition parameters were recorded and compared before and after drug administration. RESULTS Intravenous administration of NNC 26-9100 at 10, 30, 100 and 300 μg/kg (n=6 per dose) increased intercontraction intervals at doses of 30 μg/kg or higher in a dose-dependent fashion to 100.8 ± 1.1%, 116.4 ± 9.1%, 137.4 ± 7.5% and 165.1 ± 17.9% of the control value, respectively (at 30, 100 and 300 μg/kg, p<0.01). Intravenous administration of NNC 26-9100 at 10, 30, 100 and 300 μg/kg (n=6 per dose) also increased pressure threshold at doses of 30 μg/kg or higher in a dose-dependent fashion to 7.16 ± 1.23 cm H2O, 10.49 ± 1.41 cm H2O, 12.61 ± 1.17 cm H2O and 17.34 ± 1.95 cm H2O, respectively (at 30, 100 and 300 μg/kg, p<0.01). There were no significant changes in baseline pressure, maximum voiding pressure or residual urine. However, NNC 26-9100-induced increases in intercontraction intervals and pressure threshold were not seen in rats with C-fiber desensitization induced by capsaicin pretreatment. CONCLUSIONS These results indicate that activation of sst4 receptor can inhibit the micturition reflex via suppression of capsaicin sensitive C-fiber afferent pathways in rats. Thus, the sst4 receptor could be a potential target for the treatment of bladder dysfunction such as overactive bladder. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e203-e204 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information 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 Tadahiro Isoyama Yonago, Japan More articles by this author Takehiro Sejima Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Michael Chancellor Royal Oak, MI More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...