Boxall S J, Thompson S W, Dray A, Dickenson A H, Urban L
Sandoz Institute for Medical Research, London, U.K.
Neuroscience. 1996 Sep;74(1):13-20. doi: 10.1016/0306-4522(96)00101-7.
The contribution of metabotropic glutamate receptor activation to the spinal segmental reflex response evoked at high-intensity electrical stimulation suggesting a role in nociception, has been examined in an in vitro preparation of neonatal rat spinal cord. Segmental reflex responses were recorded as a ventral root depolarization evoked following drug perfusion to the spinal cord or by electrical activation of high-threshold nociceptive afferent fibres. Superfusion of the selective metabotropic glutamate receptor agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], to the spinal cord produced a dose-dependent, reversible ventral root depolarization (EC50 = 58 +/- 7 microM; n = 4), which was antagonized by the selective metabotropic glutamate receptor antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; IC50 = 243 +/- 61 microM; n = 4). MCPG, over the same concentration range (10 microM-5.0 mM) did not affect N-methyl-D-aspartate-induced ventral root depolarizations. In contrast, the specific N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) reduced N-methyl-D-aspartate-evoked ventral root depolarization but did not affect the depolarization evoked by (1S,3R)-ACPD, thus indicating the specificity of the antagonists for these aggregate responses. MCPG significantly reduced the prolonged phase of the single shock C-fibre-evoked ventral root depolarization (IC50 = 2.9 +/- 0.2 mM; n = 3-5). Low frequency high intensity stimulation of the dorsal root evoked a wind-up response, the amplitude of which was attenuated by both D-AP5 and MCPG in a dose-dependent manner. The ventral root depolarization evoked by capsaicin application (1.0 microM, 30 s) was blocked by both MCPG (IC50 = 809 +/- 35 microM; n = 4) and D-AP5 (IC50 = 143 +/- 43 microM; n = 4). These data suggest that both D-AP5 and MCPG reduced C-fibre-induced ventral root responses. In addition to N-methyl-D-aspartate receptor, metabotropic glutamate receptor activation appears to be involved in the generation of the segmental spinal reflex evoked by high-intensity stimulation in the neonatal rat spinal cord in vitro.
代谢型谷氨酸受体激活对高强度电刺激诱发的脊髓节段性反射反应的贡献表明其在伤害感受中起作用，这已在新生大鼠脊髓的体外制备中进行了研究。节段性反射反应记录为药物灌注脊髓后或高阈值伤害性传入纤维电激活后诱发的腹根去极化。将选择性代谢型谷氨酸受体激动剂（1S，3R）-1-氨基环戊烷-1,3-二羧酸[（1S，3R）-ACPD]灌注到脊髓中会产生剂量依赖性、可逆的腹根去极化（EC50 = 58±7 microM；n = 4），这被选择性代谢型谷氨酸受体拮抗剂（+）-α-甲基-4-羧基苯甘氨酸（MCPG；IC50 = 243±61 microM；n = 4）所拮抗。在相同浓度范围（10 microM - 5.0 mM）内，MCPG不影响N-甲基-D-天冬氨酸诱导的腹根去极化。相反，特异性N-甲基-D-天冬氨酸受体拮抗剂D（-）-2-氨基-5-膦酰基戊酸（D-AP5）可降低N-甲基-D-天冬氨酸诱发的腹根去极化，但不影响（1S，3R）-ACPD诱发的去极化，从而表明这些拮抗剂对这些综合反应具有特异性。MCPG显著降低了单脉冲C纤维诱发的腹根去极化的延长阶段（IC50 = 2.9±0.2 mM；n = 3 - 5）。背根的低频高强度刺激诱发了一种累加反应，其幅度被D-AP5和MCPG以剂量依赖性方式减弱。辣椒素应用（1.0 microM，30 s）诱发的腹根去极化被MCPG（IC50 = 809±35 microM；n = 4）和D-AP5（IC50 = 143±43 microM；n = 4）所阻断。这些数据表明D-AP5和MCPG均降低了C纤维诱导的腹根反应。除了N-甲基-D-天冬氨酸受体外，代谢型谷氨酸受体激活似乎还参与了体外新生大鼠脊髓中高强度刺激诱发的节段性脊髓反射的产生。
