Department of Urology, Tottori University Faculty of Medicine, Yonago, Japan.
Urology. 2012 Dec;80(6):1391.e9-13. doi: 10.1016/j.urology.2012.07.007. Epub 2012 Aug 28.
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.
研究激活生长抑素亚型 4（SST4）对大鼠排尿反射的影响。
在乌拉坦麻醉的雌性 Sprague-Dawley 大鼠（242-265g）中进行连续膀胱测压（0.04mL/min 输注率）。在建立稳定的排尿周期后，在正常大鼠或在实验前 4 天用辣椒素预处理的大鼠中静脉给予选择性 SST4 受体激动剂 NNC 26-9100。记录并比较给药前后的排尿参数。
静脉给予 NNC 26-9100（10-300μg/kg）可显著增加剂量依赖性的收缩间期。静脉给予 NNC 26-9100（10-300μg/kg）也可显著增加压力阈值呈剂量依赖性。基础压、最大排尿压或排尿后残余尿量无明显变化。然而，在预先用辣椒素处理使 C 纤维脱敏的大鼠中，未见 NNC 26-9100 引起的收缩间期和压力阈值增加。
这些结果表明，在乌拉坦麻醉大鼠中，激活 SST4 受体可通过抑制辣椒素敏感的 C 纤维传入途径抑制排尿反射。因此，SST4 受体可能是治疗 C 纤维传入介导的膀胱功能障碍的潜在靶点。
