Regan R F
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Neurosci Lett. 1996 Jul 26;213(1):9-12. doi: 10.1016/0304-3940(96)12823-8.
The neurotoxicity of the glutamate receptor agonists N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainate was quantitatively assessed in murine spinal cord and cortical cultures prepared under identical conditions. Compared with cortical neurons, spinal neurons were less vulnerable to NMDA (EC50 for 24 h exposure about 30 microM versus 10 microM in cortical cultures) and more vulnerable to AMPA (EC50 5 microM versus 12 microM) and kainate (EC50 20 microM versus 50 microM). Neurons subject to kainate-activated cobalt uptake, a marker of calcium-permeable AMPA/kainate channels, were resistant to NMDA in both systems; these cells were significantly more prevalent in spinal cord cultures. Both the AMPA/kainate antagonist GYKI-52466 and the NMDA antagonist MK-801 attenuated spinal cord neuronal loss due to glucose deprivation; however, GYKI-52466 was more effective. These results support the hypothesis that AMPA/kainate receptor activation may play a significant role in excitotoxic injury to spinal cord neurons.
在相同条件下制备的小鼠脊髓和皮质培养物中，对谷氨酸受体激动剂N-甲基-D-天冬氨酸（NMDA）、（±）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和红藻氨酸的神经毒性进行了定量评估。与皮质神经元相比，脊髓神经元对NMDA的敏感性较低（24小时暴露的半数有效浓度约为30微摩尔，而皮质培养物中为10微摩尔），对AMPA（半数有效浓度为5微摩尔，而皮质培养物中为12微摩尔）和红藻氨酸（半数有效浓度为20微摩尔，而皮质培养物中为50微摩尔）的敏感性较高。受红藻氨酸激活的钴摄取（一种钙通透性AMPA/红藻氨酸通道的标志物）影响的神经元在两个系统中均对NMDA具有抗性；这些细胞在脊髓培养物中更为普遍。AMPA/红藻氨酸拮抗剂GYKI-52466和NMDA拮抗剂MK-801均可减轻因葡萄糖剥夺导致的脊髓神经元损失；然而，GYKI-52466的效果更佳。这些结果支持以下假说：AMPA/红藻氨酸受体激活可能在脊髓神经元的兴奋性毒性损伤中起重要作用。
