Urenjak J, Obrenovitch T P
Department of Pharmacology, School of Pharmacy, University of Bradford, UK.
Neuroreport. 2000 Apr 27;11(6):1341-4. doi: 10.1097/00001756-200004270-00038.
The aim of this study was to determine in vivo which extracellular levels of kynurenic acid (KYNA) are required to control excessive NMDA receptor activation in the rat cortex. As excitotoxicity is coupled to marked ion movements, local depolarisations induced by perfusion of NMDA or quinolinic acid (QUIN) through microdialysis probes were recorded at the site of excitotoxin application. Perfusion of KYNA through the dialysis fibre inhibited the excitotoxin responses with an IC50 of 32-66 microM (extracellular concentration corrected for microdialysis delivery), but > 10-fold lower levels of endogenous KYNA were reported to be neuroprotective. Accordingly, these results strengthen the notion that KYNA accumulation may protect the brain parenchyma by acting on different molecular target(s), besides the NMDA receptor glycine site.
本研究的目的是在体内确定需要何种细胞外犬尿喹啉酸（KYNA）水平来控制大鼠皮层中过度的NMDA受体激活。由于兴奋性毒性与显著的离子运动相关联，通过微透析探针灌注NMDA或喹啉酸（QUIN）所诱导的局部去极化在兴奋性毒素施加部位被记录下来。通过透析纤维灌注KYNA可抑制兴奋性毒素反应，其半数抑制浓度（IC50）为32 - 66微摩尔（针对微透析递送校正后的细胞外浓度），但据报道内源性KYNA水平低10倍以上时仍具有神经保护作用。因此，这些结果强化了这样一种观念，即除了NMDA受体甘氨酸位点外，KYNA的积累可能通过作用于不同的分子靶点来保护脑实质。
