上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

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

杨智昉1，张颖2*，李慈珍3，刘远谋3，王红卫1   

  1. 1.上海健康医学院  基础医学院生理教研室, 上海 201318； 2.上海交通大学 基础医学院实验中心， 上海 200025； 3.上海交通大学 基础医学院生理学教研室， 上海 200025
  • 出版日期:2016-02-28 发布日期:2016-03-29
  • 通讯作者: 王红卫, 电子信箱: jywanghw@shsmu.edu.cn。
  • 作者简介:杨智昉（1969—）， 男， 副教授， 硕士; 电子信箱: yangzhifang@189.cn; 张颖（1978—）， 女， 实验师， 硕士; 电子信箱: fly0117@126.com。*为共同第一作者。
  • 基金资助:

    上海市科委重点资助项目（06JC14045）；上海市教育委员会科研创新项目（13yz150）；上海医药高等专科学校教育科研基金（2014zr006FY）

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

YANG Zhi-fang1, ZHANG Ying2*, LI Ci-zhen3, LIU Yuan-mou3, WANG Hong-wei1   

  1. 1.Department of Physiology, Basic Medicine Faculty, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China; 2.Experimental Center, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China; 3.Department of Physiology, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China
  • Online:2016-02-28 Published:2016-03-29
  • Supported by:

    Key Project of Science and Technology Commission of Shanghai Municipality, 06JC14045; Scientific Research Innovation Project of Shanghai Education Committee, 13yz150; Education and Scientific Research Foundation of Shanghai Institute of Health Sciences, 2014zr006FY

PDF (PC)

1006

摘要：

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（hSERTs）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hSERTs，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hSERTs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。

关键词: 5-羟色胺转运体, 选择性5-羟色胺重摄取阻断剂, 双微电极电压钳

Abstract:

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.

Key words: serotonin transporter, selective serotonin reuptake inhibitors, two-electrode voltage clamp