N-甲基-D-天冬氨酸受体对清醒大鼠海马谷氨酸释放的调节作用  

Regulation of Excitatory Amino Acid Release by N-Methyl-D-Aspartate Receptors in Rat Hippocampus

作　　者：金英[1] 王英[2] 刘婉珠[1] 赵艳杰[1] 

机构地区：[1]锦州医学院药理学教研室 [2]锦州市中心医院神经内科,辽宁锦州121001

出　　处：《锦州医学院学报》2004年第1期1-4,共4页Journal of Jinzhou Medical College

摘　　要：目的　应用清醒大鼠脑微透析技术 ,通过观察N -甲基 -D -天冬氨酸 (NMDA)受体激动剂和阻断剂对大鼠海马兴奋性氨基酸释放的影响 ,探讨NMDA受体对大鼠海马兴奋性氨基酸释放的自身调节作用。方法　Sprague-Dawley雄性大鼠 ,横跨海马背部植入一自制的透析探头 ,待大鼠清醒后 2 4h用人造脑脊液灌流 ,灌流速度为 5 μl·min-1,每 2 0min收集一次透析液 ,采用邻苯二甲醛 - β -巯基乙醇衍生化反相梯度洗脱荧光检测透析液中谷氨酸的含量。结果　海马内局部灌流NMDA 5 0 0 μmol·L-1可明显增加细胞外基础状态下谷氨酸水平。非竞争性NMDA受体拮抗剂MK - 80 1(10 0 μmol·L-1)可拮抗NMDA引起的谷氨酸释放增加作用。单独应用MK - 80 1(10 0 μmol·L-1)对基础状态下谷氨酸的水平没有影响。局部灌流NMDA受体协同激动剂甘氨酸5 0 0 μmol·L-1也可明显增加细胞外基础状态下谷氨酸的水平。局部灌流NMDA受体上甘氨酸部位的选择性阻断剂 7-氯犬尿烯酸 2 0 0 μmol·L-1可以拮抗甘氨酸引起的谷氨酸释放增加作用。结论　本研究发现兴奋性氨基酸受体NMDA受体的激活可增加海马内兴奋性神经递质的释放 ,这种NMDA受体可能存在于突触前膜 (兴奋性神经末梢膜上 ) ,即自身调节受体正反馈调节兴奋性氨基酸的释放。Objective The microdialysis technique was utilized to study the effect of N-methyl-D-aspartate(NMDA) receptor agonists and antagonists on the release of endogenous glutamate(Glu) from the rat hippocampus in vivo. Methods Male Sprague-Drawly rats weighing 250～300 g were anesthetized. A microdialysis probe was transversely implanted in the dorsal hippocampus. After 24 h recovery period, the microdialysis probes were perfused at 5μL·min -1 with Mg 2+ -free artificial cerebral spinal fluid. Samples were collected every 20 min following a washout period of 1 h. The concentration of Glu was determined by using a HPLC connected with a fluorometric detector. Results Local infusion of NMDA 500μmol·L -1 in hippocampus resulted in a striking increase in extracellular concentration of Glu in basal levels. The NMDA-induced increase in extracellular concentration of Glu was significantly reduced by prior perfusion with dizocolpine (Mk-801) 100μmol·L -1 , a non-competitive NMDA receptor antagonist. However, MK-801 100μmol·L -1 had no apparent influence on the basal level of Glu. Local infusion with glycine 500μmol·L -1 , a coordinate agonist at the glycine site associated to the NMDA receptor, significantly increased basal level of Glu. Such glycine-induced effects were significantly reduced by 7-Cl-kynurenic acid, a selective blocker of the glycine site located in the NMDA receptor. Conclusions It is proposed that activation of NMDA receptors by endogenous Glu increased the subsequent release of excitatory amino acids from excitatory neurons in the hippocampus.

关 键 词：N-甲基-D-天冬氨酸受体 大鼠 海马 谷氨酸释放 调节作用 脑微透析技术 自身受体 

分 类 号：R966[医药卫生—药理学]