Quesada O, Hirsch J, Ben-Ari Y, Bernard C
Instituto de Fisiología Cellular, UNAM, México, D.F., Mexico.
Neurosci Lett. 1996 Jul 19;212(3):171-4. doi: 10.1016/0304-3940(96)12803-2.
Using an animal model of temporal lobe epilepsy, the kainic acid lesioned rat hippocampus, we have evaluated the possibility of modulating glutamate N-methyl-D-aspartate (NMDA) receptor-dependent evoked epileptiform activity through the manipulation of NMDA receptor redox sites. Epileptiform activity was recorded extracellularly from hippocampal slices, in the stratum pyramidale of the CA1 area, and the effects of the oxidizing reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and the reducing agent Tris(2-carboxy ethyl)phosphine (TCEP) on these responses were quantified. Epileptiform activity was substantially reduced in the presence of DTNB but was fully reinstated with the application of TCEP. The effects of both drugs persisted even after wash. Epileptiform activity was totally abolished in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid. These results suggest that epileptiform activity can be controlled by manipulation of the redox sites of NMDA receptors and raise the possibility of developing new anticonvulsant drugs which do not fully block NMDA receptor-mediated synaptic transmission.
利用颞叶癫痫动物模型，即经 kainic 酸损伤的大鼠海马体，我们评估了通过操纵 N-甲基-D-天冬氨酸（NMDA）受体氧化还原位点来调节 NMDA 受体依赖性诱发癫痫样活动的可能性。在海马切片的 CA1 区锥体层细胞外记录癫痫样活动，并对氧化试剂 5,5'-二硫代双（2-硝基苯甲酸）（DTNB）和还原试剂三（2-羧乙基）膦（TCEP）对这些反应的影响进行定量分析。在 DTNB 存在的情况下，癫痫样活动显著降低，但在应用 TCEP 后完全恢复。即使在冲洗后，两种药物的作用仍然持续存在。在 NMDA 受体拮抗剂 D-2-氨基-5-磷酸戊酸存在的情况下，癫痫样活动完全消失。这些结果表明，癫痫样活动可以通过操纵 NMDA 受体的氧化还原位点来控制，并提高了开发不完全阻断 NMDA 受体介导的突触传递的新型抗惊厥药物的可能性。
