Anesthetics produce subunit-selective actions on glutamate receptors.
Anesthetics produce subunit-selective actions on glutamate receptors.
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发表时间：
1996-03
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通讯作者：
J. E. Dildy-Mayfield;Edmond I. Eger;R. Harris
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作者：
J. E. Dildy-Mayfield;Edmond I. Eger;R. Harris
我们评估了麻醉剂作用中特异性谷氨酸受体的参与。除了临床麻醉剂恩氟烷，异氟烷和氟烷，我们测试了新的卤代化合物，这是麻醉剂或非麻醉剂在体内，谷氨酸受体（GluR）亚基。在表达GluR 1、GluR 3、GluR 2 +3或GluR 6亚基的爪蟾卵母细胞中测试这些挥发性化合物以及戊巴比妥和苯巴比妥对红藻氨酸诱导电流的影响。麻醉剂1-氯-1，2，2-三氟环丁烷（F3）对表达GluR 3受体的卵母细胞的红藻氨酸反应有微弱的抑制作用，但对表达GluR 1或GluR 2 +3受体的卵母细胞无抑制作用。令人惊讶的是，F3增强表达红藻氨酸选择性受体GluR 6的卵母细胞中的红藻氨酸反应。非麻醉剂2，3-氯八氟丁烷（F8）和1，2-二氯六氟环丁烷（F6）不影响GluR 3或GluR 6红藻氨酸反应。在表达GluR 1、GluR 3或GluR 2 +3受体的卵母细胞中，异氟烷的抑制作用较弱，而恩氟烷和氟烷的抑制作用较弱。与F3一样，异氟烷、恩氟烷和氟烷增强了GluR 6受体的红藻氨酸诱导电流。氟烷对GluR 3和GluR 6受体的抑制和增强作用通过增加氟烷暴露的持续时间而增强。与挥发性麻醉剂的相反作用相反，戊巴比妥和苯巴比妥抑制GluR 3和GluR 6红藻氨酸反应，对GluR 6受体有更大的影响。这些结果提供了新的证据表明，麻醉剂对谷氨酸受体产生选择性作用，表明亚基组成可能决定谷氨酸受体在麻醉中的作用。
We assessed the involvement of specific glutamate receptors in the action of anesthetics. In addition to the clinical anesthetics enflurane, isoflurane and halothane, we tested novel halogenated compounds, which are anesthetic or nonanesthetic in vivo, on glutamate receptor (GluR) subunits. these volatile compounds as well as pentobarbital and phenobarbital were tested on kainate-induced currents in Xenopus oocytes expressing GluR1, GluR3, GluR2+3 or GluR6 subunits. The anesthetic 1-chloro-1,2,2-triflurocyclobutane (F3) weakly inhibited kainate responses in oocytes expressing GluR3 receptors but not oocytes expressing GluR1 or GluR2+3 receptors. Surprisingly, F3 potentiated kainate responses in oocytes expressing the kainate-selective receptor GluR6. The nonanesthetics 2,3-chlorooctafluorobutane (F8) and 1,2-dichlorohexafluorocyclobutane (F6) did not affect GluR3 or GluR6 kainate responses. Isoflurane weakly inhibited although enflurane and halothane modestly inhibited kainate responses in oocytes expressing GluR1, GluR3 or GluR2+3 receptors. As with F3, isoflurane, enflurane and halothane potentiated kainate-induced currents of GluR6 receptors. The respective inhibitory and potentiating effects of halothane on GluR3 and GluR6 receptors were enhanced by increasing duration of halothane exposure. In contrast to the opposing action of volatile anesthetics, pentobarbital and phenobarbital inhibited GluR3 and GluR6 kainate responses and had a much greater effect on GluR6 receptors. These results provide novel evidence that anesthetics produce selective actions on glutamate receptors, suggesting that subunit composition may determine the role of glutamate receptors in anesthesia.