Inhibitory Effect of Somatostatin Receptor Subtype-4 Agonist NNC 26-9100 on Micturition Reflex in Rats

Abstract

To investigate the effects of activation of somatostatin subtype 4 (SST4) on the micturition reflex in rats. 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. 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. 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.