Clozapine inhibits strychnine-sensitive glycine receptors in rat hippocampal neurons
Clozapine inhibits strychnine-sensitive glycine receptors in rat hippocampal neurons
复制标题
氯氮平抑制大鼠海马神经元马钱子碱敏感甘氨酸受体
DOI：
10.1016/j.brainres.2009.04.043
复制
发表时间：
2009-06-30
期刊：
影响因子：
2.9
通讯作者：
Zhao, Jingping
中科院分区：
文献类型：
--
作者：
Liu, Yong;Hu, Changping;Zhao, Jingping
癫痫发作是氯氮平治疗过程中的一种严重副作用，但其发生机制尚不完全清楚。士的宁敏感性甘氨酸受体（GlyRs）在调节海马兴奋性中起重要作用。在本研究中，我们研究了Clo对培养的大鼠海马神经元GlyRs的影响。Clo以浓度依赖性方式可逆地抑制甘氨酸诱导的氯电流（I-Gly）。单独甘氨酸的半数最大效应浓度（EC 50）为25.6 +/- 0.7 μ M，希尔系数为1.5 +/- 0.1;在Clo存在下，EC 50和希尔系数分别为28.9 +/- 6.3 μ M和1.2 +/- 0.3，Clo对这两个数值没有显著影响。此外，Clo抑制I-Gly不受氟哌啶醇（Hal）阻断D-1和D-2多巴胺受体的影响。总之，这些结果表明，Clo是GlyR的非竞争性拮抗剂，不依赖于其多巴胺受体的激活，这可能有助于与Clo治疗相关的癫痫发作。(C)2009爱思唯尔有限公司版权所有。
Seizure is one kind of severe side effects during clozapine (Clo) treatment, However, the mechanism of seizure associated with Clo therapy is not completely clear. Strychnine-sensitive glycine receptors (GlyRs) play an important role in regulating the excitability in the hippocampus. In the present study, we investigated the effect of Clo on GlyRs in cultured hippocampal neurons of rats. Clo reversibly inhibited the glycine-induced chloride currents (I-Gly) in a concentration-dependent manner. The half-maximal effect concentration (EC50) for glycine alone was 25.6 +/- 0.7 mu M with the Hill coefficient 1.5 +/- 0.1; in the presence of Clo, the EC50 and the Hill coefficient were 28.9 +/- 6.3 mu M and 1.2 +/- 0.3 respectively, which were not significantly affected by Clo. In addition, Clo inhibition of I-Gly was not influenced by blocking D-1 and D-2 dopamine receptors with haloperidol (Hal). Taken together, these results suggest that Clo is a non-competitive antagonist of GlyR independent of its activation of dopamine receptors, which may contribute to seizure associated with Clo therapy. (C) 2009 Elsevier B.V. All rights reserved.