Barbour B, Szatkowski M, Ingledew N, Attwell D
Department of Physiology, University College London, UK.
Nature. 1989;342(6252):918-20. doi: 10.1038/342918a0.
Activation of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus, possibly by blocking glutamate uptake. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid could severely compromise glutamate uptake and thus contribute to neuronal death.
神经递质谷氨酸激活N-甲基-D-天冬氨酸（NMDA）受体，刺激磷脂酶A2释放花生四烯酸。这种第二信使可能通过阻断谷氨酸摄取，促进海马体中谷氨酸能突触的长期增强。我们使用全细胞膜片钳技术电监测摄取，研究了花生四烯酸对胶质细胞摄取谷氨酸的影响。微摩尔水平的花生四烯酸抑制谷氨酸摄取，主要是通过降低最大摄取速率，而对外部谷氨酸和钠的亲和力影响较小。去除花生四烯酸后，会有一个快速（5分钟）的部分恢复阶段，随后是持续至少20分钟的摄取抑制。令人惊讶的是，花生四烯酸的作用不受环氧化酶或脂氧化酶抑制剂的影响，这表明它可能通过增加膜流动性直接抑制摄取。由于磷脂酶A2的阻断会阻止长期增强（LTP）的诱导，花生四烯酸对谷氨酸摄取的抑制可能有助于LTP中发生的突触增益增加。在缺氧期间，花生四烯酸的释放可能严重损害谷氨酸摄取，从而导致神经元死亡。
