Bondy S C, Lee D K
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Brain Res. 1993 May 7;610(2):229-33. doi: 10.1016/0006-8993(93)91405-h.
The effect of various selective glutamate agonists upon the rate of generation of reactive oxygen species (ROS), was examined in an isolated synaptoneurosomal (microsac) fraction derived from rat cerebral cortex. The rates of ROS generation were determined by a fluorescent probe. Agonists specific for each of the three major glutamate inotropic receptor sites (NMDA, kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxalolpropionic acid, AMPA), were able to enhance rates of ROS generation. The metabotropic glutamate agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid, (ACPD), was inactive in this regard. Stimulation of ROS was most pronounced in the case of kainate. Such results could not be replicated by use of ion-channel active agents, veratridine and A23817. Pretreatment with the kainate antagonist, 6-cyano-7-quinoxaline-2,3-dione (CNQX), was not able to block the kainate-induced elevation of ROS. Domoic acid, a kainate agonist, also enhanced microsac ROS generation. Neurological damage may result from generation of excess free radicals, and this may be effected by glutamate agonists acting by means independent of their ionotropic properties.
在源自大鼠大脑皮层的分离突触体神经小体（微囊）组分中，研究了各种选择性谷氨酸激动剂对活性氧（ROS）生成速率的影响。ROS的生成速率由荧光探针测定。对三种主要的离子型谷氨酸受体位点（N-甲基-D-天冬氨酸、海人酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸，AMPA）各自具有特异性的激动剂，均能够提高ROS的生成速率。代谢型谷氨酸激动剂反式-1-氨基环戊烷-1,3-二羧酸（ACPD）在这方面无活性。在海人酸的情况下，ROS的刺激最为明显。使用离子通道活性剂藜芦碱和A23187无法重复这样的结果。用海人酸拮抗剂6-氰基-7-喹喔啉-2,3-二酮（CNQX）预处理，无法阻断海人酸诱导的ROS升高。海人酸激动剂软骨藻酸也增强了微囊ROS的生成。过量自由基的产生可能导致神经损伤，这可能由谷氨酸激动剂通过与其离子型特性无关的方式起作用而实现。
