Effects of antidepressants on P2X7 receptors
Effects of antidepressants on P2X7 receptors
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DOI：
10.1016/j.psychres.2016.06.001
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发表时间：
2016-08
影响因子：
11.3
通讯作者：
Wei Wang;Z. Xiang;Chunfeng Jiang;Wei-Zhi Liu;Zhi-lei Shang
中科院分区：
文献类型：
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作者：
Wei Wang;Z. Xiang;Chunfeng Jiang;Wei-Zhi Liu;Zhi-lei Shang
抗抑郁药包括帕罗西汀、氟西汀和地昔帕明通常用于治疗抑郁症。P2×7受体是P2 X家族的成员。最近的研究表明，这些受体可能构成治疗抑郁症的新的潜在靶点。在本研究中，我们使用全细胞膜片钳技术检测了这些抗抑郁药对在人胚肾（HEK）293细胞中稳定表达的克隆大鼠P2×7受体的作用，并发现10 μM剂量的帕罗西汀可显著降低P2×7受体激动剂BzATP在预孵育6-12小时后诱发的内向电流，但急性应用则无此作用（10 μM）或以1 μM、3 μM或10 μM帕罗西汀的剂量预孵育2-6 h。无论是氟西汀还是地昔帕明对急性应用或不同浓度预孵育BzATP诱发的电流均无显著影响。这些结果表明，大鼠P2×7受体对抗抑郁药的敏感性是不同的，这可能代表了这些药物发挥其疗效和副作用的未知机制。
Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10 µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6–12 but not by acute application (10 µM) or pre-incubation for 2–6 h at a dose of 1 µM, 3 µM or 10 µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects.