title: Inhibitory effect of somatostatin receptor subtype-4 agonist NNC 26-9100 on micturition reflex in rats.
abstract: OBJECTIVE
  To investigate the effects of activation of somatostatin subtype 4 (SST4) on the micturition reflex in rats.
  
  
  METHODS
  Continuous cystometrograms (0.04 mL/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. The micturition parameters were recorded and compared before and after drug administration.
  
  
  RESULTS
  Intravenous administration of NNC 26-9100 (10-300 μg/kg) significantly increased the intercontraction interval in a dose-dependent fashion. Intravenous administration of NNC 26-9100 (10-300 μg/kg) also significantly increased the pressure threshold in a dose-dependent fashion. No significant changes were seen in the baseline pressure, maximum voiding pressure, or postvoid residual urine volume. However, NNC 26-9100-induced increases in the intercontraction intervals and pressure threshold were not seen in rats with C-fiber desensitization induced by capsaicin pretreatment.
  
  
  CONCLUSIONS
  These results indicate that in urethane-anesthetized rats, activation of the SST4 receptor can inhibit the micturition reflex by suppression of capsaicin-sensitive C-fiber afferent pathways. Thus, the SST4 receptor could be a potential target for the treatment of C-fiber afferent-mediated bladder dysfunction.
authors.affiliation: Department of Urology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Honda
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hinata
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000819:agonists*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014554:Urination / Q000187:drug effects* / Q000502:physiology
chemical_list: D000631:Aminopyridines; C115929:NNC 26-9100; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D013004:Somatostatin; D013890:Thiourea; D002211:Capsaicin