卵母细胞异体表达模型中选择性5-HT重摄取阻断剂的电生理特性比较

Comparison of electrophysiological properties of selective serotonin reuptake inhibitors in heterologously expressed model of oocytes

目的观察和研究选择性5-羟色胺(5-HT)重摄取阻断剂(SSRIs)西酞普兰、氟西汀、帕罗西汀与非典型四环类抗抑郁药曲唑酮对人5-HT转运体(h SERTs)重摄取5-HT的抑制效应。方法在非洲爪蟾卵母细胞上异体表达h SERTs,采用双微电极电压钳技术记录在不同药物作用下5-HT转运电流的变化。结果在相同浓度下,帕罗西汀、西酞普兰、氟西汀和曲唑酮分别使5-HT诱导的初始转运电流抑制了(29.31±1.52)%、(47.17±3.38)%、(27.72±2.01)%和(43.30±2.83)%,但曲唑酮在其作用时间内未能有效逆转5-HT转运电流。采用指数衰减函数拟合电流曲线求取药物与h SERTs的结合时间常数以及药物与5-HT竞争转运体的时间常数,发现在3种SSRIs中,帕罗西汀的结合与竞争时间常数均最小,然后依次为氟西汀和西酞普兰。结论帕罗西汀对5-HT转运电流的初始抑制效果优于氟西汀和西酞普兰。

Objective To observe and explore the inhibitory effect of selective serotonin reuptake inhibitors（SSRIs） citalopram,fluoxetine,and paroxetine and the atypical anti-depressant drug trazodone on the human serotonin transporters（hSERTs）.Methods hSERTs were transfected into the oocytes of African Xenopus laevis to establish a heterologous expression system.Two-electrode voltage clamp technique was used to record the changes of 5-HT-induced transport current under the action of different drugs.Results The same concentration of paroxetine,citalopram,fluoxetine,and trazodone inhibited the 5-HT-induced initial transport current by（29.31 ±1.52）%,（47.17 ±3.38）%,（27.72 ±2.01）%,and（43.30 ±2.83）%,respectively.But trazodone failed to efficiently reverse the 5-HT-induced transport current within its action time.The binding time constants between drugs and hSERTs and competition time constants between drugs and 5-HT were calculated by fitting current curves with the exponential decay function.Among three SSRIs,binding and competition time constants of paroxentine were the smallest,followed by fluoxentine and citalopram.Conclusion The initial inhibition effect of paroxetine on 5-HT-induced transport current is better than that of fluoxentine and citalopram.