Mixcoatl-Zecuatl Teresa, Flores-Murrieta Francisco J, Granados-Soto Vinicio
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Coapa, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330, México, DF, Mexico.
Eur J Pharmacol. 2006 Feb 15;531(1-3):87-95. doi: 10.1016/j.ejphar.2005.12.006. Epub 2006 Jan 24.
The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG) pathway on gabapentin-induced spinal antiallodynic activity was assessed in spinal nerve injured rats. Intrathecal gabapentin, diazoxide or pinacidil reduced tactile allodynia in a dose-dependent manner. Pretreatment with NG-L-nitro-arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase NOS), 7-nitroindazole (neuronal NO synthase inhibitor), 1H-[1,2,4] -oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor) or (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo-[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor), but not NG-D-nitro-arginine methyl ester (D-NAME) or okadaic acid (protein phosphatase 1 and 2 inhibitor) prevented gabapentin-induced antiallodynia. Pinacidil activity was not blocked by L-NAME, D-NAME, 7-nitroindazole, ODQ, KT-5823 or okadaic acid. Moreover, KT-5823, glibenclamide (ATP-sensitive K+ channel blocker), apamin and charybdotoxin (small- and large-conductance Ca2+-activated K+ channel blockers, respectively), but not margatoxin (voltage-gated K+ channel blocker), L-NAME, 7-nitroindazole, ODQ or okadaic acid, reduced diazoxide-induced antiallodynia. Data suggest that gabapentin-induced spinal antiallodynia could be due to activation of the NO-cyclic GMP-PKG-K+ channel pathway.
在脊髓神经损伤大鼠中评估了一氧化氮（NO）-环磷酸鸟苷-蛋白激酶G（PKG）通路在加巴喷丁诱导的脊髓抗痛觉过敏活性中的可能作用。鞘内注射加巴喷丁、二氮嗪或匹那地尔可剂量依赖性地减轻触觉异常性疼痛。用NG-L-硝基精氨酸甲酯（L-NAME，一氧化氮合酶NOS的非特异性抑制剂）、7-硝基吲唑（神经元型一氧化氮合酶抑制剂）、1H-[1,2,4] -恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，鸟苷酸环化酶抑制剂）或（9S,10R,12R）-2,3,9,10,11,12-六氢-10-甲氧基-2,9-二甲基-1-氧代-9,12-环氧-1H-二吲哚并-[1,2,3-fg:3',2',1'-kl]吡咯并[3,4-i][1,6]苯并二氮杂卓-10-羧酸甲酯（KT-5823，特异性PKG抑制剂）预处理，但NG-D-硝基精氨酸甲酯（D-NAME）或冈田酸（蛋白磷酸酶1和2抑制剂）不能预防加巴喷丁诱导的抗痛觉过敏。匹那地尔的活性不受L-NAME、D-NAME、7-硝基吲唑、ODQ、KT-5823或冈田酸的阻断。此外，KT-5823、格列本脲（ATP敏感性钾通道阻滞剂）、蜂毒明肽和大电导钙激活钾通道阻断剂（分别为小电导和大电导钙激活钾通道阻滞剂）可减轻二氮嗪诱导的抗痛觉过敏，但玛格毒素（电压门控钾通道阻滞剂）、L-NAME、7-硝基吲唑、ODQ或冈田酸则不能。数据表明，加巴喷丁诱导的脊髓抗痛觉过敏可能是由于NO-环磷酸鸟苷-PKG-钾通道通路的激活。
