Minami Toshiaki, Nishihara Isao, Uda Rumiko, Ito Seiji, Hyodo Masayoshi, Hayaishi Osamu
Department of Anesthesiology, Osaka Medical College, TakatsukiJapan Department of Cell Biology, Osaka Bioscience Institute, SuitaJapan.
Pain. 1994 May;57(2):225-231. doi: 10.1016/0304-3959(94)90227-5.
In order to investigate the involvement of glutamate receptor systems in allodynia induced by prostaglandin (PG) E2 or F2 alpha, we co-administered antagonists for N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors intrathecally with PGE2 or PGF2 alpha and examined their effects on the allodynia evoked in conscious mice by non-noxious brushing of the flanks. MK-801, a non-competitive NMDA receptor channel blocker, and D-AP-5, a selective NMDA receptor antagonist, dose-dependently blocked PGE2-induced allodynia with an IC50 of 1.60 and 0.52 microgram/mouse, respectively. A glycine binding-site antagonist for the NMDA receptor, 7-Cl-KYNA, did not influence it. None of these NMDA receptor antagonists inhibited PGF2 alpha-evoked allodynia. Non-NMDA receptor antagonists GAMS and CNQX inhibited both PGE2- and PGF2 alpha-induced allodynia. On the other hand, L-AP-3 and L-AP-4, putative metabotropic glutamate receptor antagonists, dose-dependently antagonized the allodynia induced by PGF2 alpha with an IC50 of 0.92 and 3.26 ng/mouse, respectively, but not that induced by PGE2. Intrathecal administration of L-glutamate produced allodynia over a wide range of low doses from 0.1 pg to 0.1 microgram/mouse, and the maximal effect was observed at 1 ng. Similar to allodynia induced by prostaglandins, the response lasted over a 50-min experimental period. These results demonstrate that both PGE2- and PGF2 alpha-evoked allodynia are mediated through a pathway that includes the glutamate receptor system but that subtypes of glutamate receptors involved and sites of action in the spinal cord may be different between them.
为了研究谷氨酸受体系统在前列腺素（PG）E2或F2α诱导的异常性疼痛中的作用，我们将N-甲基-D-天冬氨酸（NMDA）、非NMDA或代谢型谷氨酸受体拮抗剂与PGE2或PGF2α鞘内联合给药，并检测它们对清醒小鼠胁腹非伤害性轻刷诱发的异常性疼痛的影响。非竞争性NMDA受体通道阻滞剂MK-801和选择性NMDA受体拮抗剂D-AP-5剂量依赖性地阻断PGE2诱导的异常性疼痛，IC50分别为1.60和0.52微克/小鼠。NMDA受体的甘氨酸结合位点拮抗剂7-Cl-KYNA对其无影响。这些NMDA受体拮抗剂均未抑制PGF2α诱发的异常性疼痛。非NMDA受体拮抗剂GAMS和CNQX抑制PGE2和PGF2α诱导的异常性疼痛。另一方面，假定的代谢型谷氨酸受体拮抗剂L-AP-3和L-AP-4剂量依赖性地拮抗PGF2α诱导的异常性疼痛，IC50分别为0.92和3.26纳克/小鼠，但不拮抗PGE2诱导的异常性疼痛。鞘内注射L-谷氨酸在0.1皮克至0.1微克/小鼠的广泛低剂量范围内产生异常性疼痛，在1纳克时观察到最大效应。与前列腺素诱导的异常性疼痛相似，该反应在50分钟的实验期内持续存在。这些结果表明，PGE2和PGF2α诱发的异常性疼痛均通过包括谷氨酸受体系统的途径介导，但所涉及的谷氨酸受体亚型和脊髓中的作用位点在它们之间可能不同。
