Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Department of Urology, Hamamatsu University School of Medicine , Hamamatsu , Japan.
Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F79-F85. doi: 10.1152/ajprenal.00614.2017. Epub 2018 Feb 14.
To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT agonist) or LP44 (a 5-HT agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmHO and UBP by 13.3 cmHO compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmHO and UBP by 15.1 cmHO, and LP44 also increased A-URS by 20.6 cmHO and UBP by 11.4 cmHO compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmHO in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmHO, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT antagonist) and SB-269970 (a selective 5-HT antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT and 5-HT receptors.
为了阐明 5-羟色胺（5-HT）在打喷嚏时预防压力性尿失禁（SUI）中的作用，我们使用雌性大鼠研究了腹腔内给予对氯苯丙氨酸（PCPA；5-HT 合成抑制剂）和静脉内给予 CP-809101（5-HT 激动剂）或 LP44（5-HT 激动剂）的效果，在这些大鼠中，我们检查了打喷嚏时神经诱发的控尿反射。在正常成年雌性大鼠中，或在给予药物后，测量打喷嚏时尿道压力反应幅度（A-URS）、尿道中段基础压（UBP）和打喷嚏诱发漏尿点压（S-LPP）。与正常大鼠相比，PCPA 使 A-URS 降低了 35.1cmH2O，UBP 降低了 13.3cmH2O。在给予 PCPA 的大鼠中，CP-809101 使 A-URS 增加了 24.1cmH2O，UBP 增加了 15.1cmH2O，LP44 也使 A-URS 增加了 20.6cmH2O，UBP 增加了 11.4cmH2O，与单独给予 PCPA 的大鼠相比。在给予 PCPA 的大鼠中，S-LPP 为 40.1cmH2O 时出现 SUI，CP-809101 和 LP44 分别使 S-LPP 增加了 28.0 和 15.2cmH2O，与单独给予 PCPA 的大鼠相比。CP-809101 和 LP44 的作用分别被 SB-242084（5-HT 选择性拮抗剂）和 SB-269970（5-HT 选择性拮抗剂）拮抗。这些结果表明，5-HT 受体的激活增强了打喷嚏时主动尿道闭合反射，至少部分是通过 5-HT 和 5-HT 受体。
