Yang L C, Marsala M, Yaksh T L
Department of Anesthesiology, Chang Gung Memorial Hospital, Kaohsiung Hsien, Taiwan, R.O.C.
Neuroscience. 1996 Nov;75(2):453-61. doi: 10.1016/0306-4522(96)00294-1.
Current work has shown that spinal excitatory amino acid receptor activation can evoke physiological phenomena that may be mediated by the subsequent depolarization of glutamate-containing neurons and the activation of cyclo-oxygenase systems. To investigate this phenomenon, rats were implanted with lumbar intrathecal loop dialysis catheters for perfusion and an additional lumbar intrathecal PE-10 catheter for drug delivery. Two days after implantation, kainic acid (1 microgram) was injected intrathecally under light (0.5%) halothane anaesthesia and the spinal release of several amino acids and prostaglandin E2 was examined. Resting concentrations (mean expressed as pmol/25 microliters) of glutamate (89), aspartate (9), serine (387), glycine (597), taurine (185), asparagine (113) and prostaglandin E2 (0.43) were observed. Intrathecal kainic acid produced significant signs of arousal in the rat and evoked a significant increase (mean +/- S.E.M. of % baseline concentration) in aspartate (445 +/- 127%) and glutamate (221 +/- 35%). Prostaglandin E2 concentration was increased in the second post-injection sample (180 +/- 36%). Intrathecal pretreatment with 6-cyano-7-nitroquinoxaline-2, 3-dione (3 micrograms or 10 micrograms), a non-N-methyl-D-aspartate receptor antagonist, blocked amino acid but not prostaglandin E2 release after kainic acid injection. Pretreatment with MK-801 (10 micrograms; non-competitive NMDA receptor antagonist) had no significant effect on evoked release of amino acids or prostaglandin E2. Indomethacin (10 micrograms, a cyclo-oxygenase inhibitor) pretreatment significantly decreased baseline prostaglandin E2 release in control animals (61 +/- 6%) and suppressed kainic acid-evoked aspartate, taurine and prostaglandin E2 release, but had no effect on the concentration of glutamate after kainic acid injection. These data suggest that activation of spinal kainic acid receptors provides a powerful stimulus for secondary excitatory amino acid release and, consistent with the concurrent appearance of prostaglandin E2, that this release is potentiated by the release of a cyclo-oxygenase product.
目前的研究表明，脊髓兴奋性氨基酸受体激活可引发一些生理现象，这些现象可能由含谷氨酸的神经元随后的去极化以及环氧化酶系统的激活介导。为了研究这一现象，给大鼠植入腰段鞘内环路透析导管用于灌注，并额外植入一根腰段鞘内PE - 10导管用于给药。植入后两天，在轻度（0.5%）氟烷麻醉下鞘内注射 kainic 酸（1微克），并检测几种氨基酸和前列腺素E2在脊髓中的释放情况。观察到谷氨酸（89）、天冬氨酸（9）、丝氨酸（387）、甘氨酸（597）、牛磺酸（185）、天冬酰胺（113）和前列腺素E2（0.43）的静息浓度（以pmol/25微升表示的平均值）。鞘内注射 kainic 酸在大鼠中产生了明显的觉醒迹象，并使天冬氨酸（445±127%）和谷氨酸（221±35%）显著增加（相对于基线浓度的平均值±标准误）。在注射后的第二个样本中，前列腺素E2浓度升高（180±36%）。用非N - 甲基 - D - 天冬氨酸受体拮抗剂6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（3微克或10微克）进行鞘内预处理，可阻断 kainic 酸注射后氨基酸的释放，但不影响前列腺素E2的释放。用MK - 801（10微克；非竞争性NMDA受体拮抗剂）预处理对诱发的氨基酸或前列腺素E2释放没有显著影响。吲哚美辛（10微克，一种环氧化酶抑制剂）预处理显著降低了对照动物的基线前列腺素E2释放（61±6%），并抑制了 kainic 酸诱发的天冬氨酸、牛磺酸和前列腺素E2释放，但对 kainic 酸注射后谷氨酸的浓度没有影响。这些数据表明，脊髓 kainic 酸受体的激活为继发性兴奋性氨基酸释放提供了强大的刺激，并且与前列腺素E2的同时出现一致，这种释放被一种环氧化酶产物的释放所增强。
