氯氮平直接作用于GABAB受体的证据。
Evidence that clozapine directly interacts on the GABAB receptor.
作者信息
Wu Ying, Blichowski Monica, Daskalakis Zafiris J, Wu Zhouyou, Liu Chun C, Cortez Miguel A, Snead Orlando Carter
机构信息
Program in Neuroscience and Mental Health, University of Toronto fCentre for Addiction and Mental Health, Toronto, Ontario, Canada.
出版信息
Neuroreport. 2011 Sep 14;22(13):637-41. doi: 10.1097/WNR.0b013e328349739b.
Neurophysiological studies suggest that clozapine may facilitate γ-aminobutyric acid (GABAergic) neurotransmission. Therefore, we studied the interaction between clozapine and the GABAB receptor (GABABR). We showed that clozapine, and not N-desmethylclozapine, which is a metabolite of clozapine, increased the binding of the GABABR antagonist, [³H]-CGP54626A, at GABABRs. Linear regression analysis showed that the correlation between the dose of clozapine and the increase of [³H]-CGP54626A binding was significant. The curve of specific [³H]-CGP54626A binding in competition with different concentrations of GABA was left shifted in the presence of clozapine. With HEK293 cells overexpressing GABABR, we showed that clozapine had a significant increase of [³H]-CGP54626A binding at GABABR1 subunit, which provided a clue of the potential therapeutic target of clozapine.
神经生理学研究表明，氯氮平可能会促进γ-氨基丁酸（GABA能）神经传递。因此，我们研究了氯氮平与GABAB受体（GABABR）之间的相互作用。我们发现，氯氮平而非其代谢产物N-去甲基氯氮平，可增加GABABR拮抗剂[³H]-CGP54626A与GABABRs的结合。线性回归分析表明，氯氮平剂量与[³H]-CGP54626A结合增加之间的相关性显著。在氯氮平存在的情况下，与不同浓度GABA竞争的特异性[³H]-CGP54626A结合曲线向左移动。在过表达GABABR的HEK293细胞中，我们发现氯氮平使[³H]-CGP54626A与GABABR1亚基的结合显著增加，这为氯氮平的潜在治疗靶点提供了线索。
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