Nellgård B, Wieloch T
Laboratory for Experimental Brain Research, Lund University Hospital, Sweden.
Acta Physiol Scand. 1992 Dec;146(4):497-503. doi: 10.1111/j.1748-1716.1992.tb09451.x.
The effect of different glutamate-receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non-competitive N-methyl-D-aspartate (NMDA)-receptor blocker, (+-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imi ne maleate (dizocilpine or MK-801), (0.30 mumol kg-1 (0.10 mg kg-1)), and the competitive NMDA-receptor antagonists; cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), (3.36 mumol kg-1 (0.75 mg kg-1)), D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116), (1.20 mumol kg-1 (0.25 mg kg-1)) and its carboxylester CGP 43487, (6.30 mumol kg-1 (1.50 mg kg-1)). The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepripriate (AMPA)-receptor blocker, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), administered as an intravenous dose of 29.76 and 89.29 mumol kg-1 (10 & 30 mg kg-1), which is sufficient to block seizures and protect against ischaemic brain damage, did not inhibit spreading depression. None of the drugs utilized inhibited the anoxic membrane depolarization. The data demonstrate that NMDA-receptor activation is essential for the initiation and propagation of spreading depression, while activation of AMPA-receptors is not obligatory. The observed initiation and propagation of SD, during AMPA-receptor blockade, suggest that activation of voltage-operated ion channels may contribute to release the magnesium block of the NMDA-receptor operated channel and to the initiation of SD.
在麻醉大鼠中研究了不同谷氨酸受体拮抗剂对诱导莱奥皮质扩散性抑制和皮质缺氧膜去极化的影响。通过机械刺激皮质表面诱发的扩散性抑制（SD），可被非竞争性N-甲基-D-天冬氨酸（NMDA）受体阻滞剂马来酸（±）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（地佐环平或MK-801）（0.30 μmol·kg⁻¹（0.10 mg·kg⁻¹））以及竞争性NMDA受体拮抗剂顺式-4-膦酰甲基-2-哌啶羧酸（CGS 19755）（3.36 μmol·kg⁻¹（0.75 mg·kg⁻¹））、D-（E）-2-氨基-4-甲基-5-膦酰基-3-戊烯酸（CGP 40116）（1.20 μmol·kg⁻¹（0.25 mg·kg⁻¹））及其羧酸酯CGP 43487（6.30 μmol·kg⁻¹（1.50 mg·kg⁻¹））抑制。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体阻滞剂2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）静脉注射剂量为29.76和89.29 μmol·kg⁻¹（10和30 mg·kg⁻¹），该剂量足以阻断癫痫发作并预防缺血性脑损伤，但不抑制扩散性抑制。所使用药物均未抑制缺氧膜去极化。数据表明，NMDA受体激活对于扩散性抑制的起始和传播至关重要，而AMPA受体激活并非必需。在AMPA受体阻断期间观察到的SD起始和传播表明，电压门控离子通道的激活可能有助于解除NMDA受体操纵通道的镁阻滞并引发SD。
