Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats.
Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats.
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5-HT2c 受体激动剂对雌性大鼠尿道闭合机制的影响。
DOI：
10.1002/nau.23586
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Sinohara Nobuo
中科院分区：
文献类型：
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作者：
Ouchi Mifuka;Kitta Takeya;Kanno Yukiko;Higuchi Madoka;Togo Mio;Moriya Kinmihiko;Sinohara Nobuo
目的5-羟色胺（5-HT 2c）受体参与压力性尿失禁模型的尿道闭合机制。氯卡色林（Belviq®）已获得食品和药物管理局批准用于治疗肥胖症。然而，目前尚不清楚这种选择性5-HT 2c受体激动剂是否能增强压力性尿失禁（SUI）模型的尿道闭合。因此，我们研究氯卡色林是否可以增强阴道扩张（VD）雌性大鼠的尿道闭合。方法正常雌性大鼠和VD诱导的压力性尿失禁大鼠进行了测试。我们评价了单次给予氯卡色林（0.03、0.3或0.9 mg/kg，累积给药）对电刺激期间尿道压力幅度（A-URE）和尿道基线压力（UBP）的影响。结果在VD大鼠中，单次静脉注射氯卡色林（0.3和0.9 mg/kg）与生理盐水相比，A‐URE和LPP均显著增加（P< 0.05）。在正常大鼠中，与生理盐水相比，静脉注射氯卡色林（0.3和0.9 mg/kg）也显著增加了A-URE和LPP（P< 0.05）。A‐URE和LPP的变化，这是主动尿道闭合的参数，在正常大鼠比VD rates.ConclusionsWe表明，氯卡色林可以激活尿道外括约肌和盆底肌肉，这表明主动闭合机制的影响。5-HT 2c受体激动剂可能对SUI患者具有双重作用，不仅可以减少肥胖，还可以增强主动尿道闭合。
AimsThe serotonin (5‐HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity. However, it is unclear whether this selective 5‐HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD).MethodsNormal female rats and rats with stress incontinence induced by VD were tested. We evaluated the effect of a single dose of lorcaserin (0.03, 0.3, or 0.9 mg/kg with cumulative administration) on the urethral pressure amplitude during electrical stimulation (A‐URE) and on the urethral baseline pressure (UBP). The manual compression‐induced leak point pressure (LPP) was also measured.ResultsIn VD rats, a single intravenous injection of lorcaserin (0.3 and 0.9 mg/kg) significantly increased both A‐URE and LPP compared to saline (P< 0.05). In normal rats, intravenous lorcaserin (0.3 and 0.9 mg/kg) also significantly increased A‐URE and LPP compared to saline (P< 0.05). The changes of A‐URE and LPP, which are parameters of active urethral closure, were significantly larger in normal rats than in VD rats.ConclusionsWe showed that lorcaserin can activate the external urethral sphincter and pelvic floor muscles, suggesting an influence on active closure mechanisms. 5‐HT2c receptors agonists may have dual effects in patients with SUI, not only by reducing obesity but also by enhancing active urethral closure.