Mefloquine blockade of Pannexin1 currents: resolution of a conflict.
Mefloquine blockade of Pannexin1 currents: resolution of a conflict.
复制标题
DOI：
10.3109/15419061003642618
复制
发表时间：
2009-12
影响因子：
--
通讯作者：
Scemes E
中科院分区：
文献类型：
--
作者：
Iglesias R;Spray DC;Scemes E
我们的实验室报告了抗疟疾奎宁衍生物甲氟喹对Pannexin1 （Panx1）电流的有效阻断。然而，其他实验室发现Panx1电流或可归因于这些通道的过程很少或没有甲氟喹敏感性。为了解决这个问题，我们对Panx1转染的神经母细胞瘤（Neuro2A）和大鼠胰岛素瘤（Rin）细胞进行了广泛的剂量反应研究，比较了从三个供应商获得的甲氟喹，并比较了对非对映体的敏感性。结果表明，对(−)-三o-(11R/2R)非对映异构体的敏感性比红血球对映异构体的敏感性差20倍，而（±）-红血球-(R*/S*)-甲氟喹的效价要低得多。这种明显较低的疗效可能解释了不同实验室将其应用于Panx1研究的结果差异。
Our laboratory has reported potent block of Pannexin1 (Panx1) currents by the antimalarial quinine derivative mefloquine. However, other laboratories have found little or no mefloquine sensitivity of Panx1 currents or processes attributable to these channels. In order to resolve this issue, we have performed extensive dose-response studies on Panx1 transfected neuroblastoma (Neuro2A) and rat insulinoma (Rin) cells comparing mefloquine obtained from three suppliers and also comparing the sensitivity to diastereomers. Results indicate a twenty-fold difference in sensitivity to the (−)-threo-(11R/2R) diastereomer compared to the erythro enatiomers and much lower potency of (±)-erythro-(R*/S*)-mefloquine obtained from one of the commercial sources. This markedly lower efficacy presumably accounts for the disparity in results from different laboratories who have applied it in Panx1 studies.