The peripheral antinociceptive with activation of effect of resveratrol is associated potassium channels
The peripheral antinociceptive with activation of effect of resveratrol is associated potassium channels
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DOI：
10.1016/s0028-3908(02)00130-2
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发表时间：
2002-10-01
影响因子：
4.7
通讯作者：
Ortiz, MI
中科院分区：
文献类型：
--
作者：
Granados-Soto, V;Argüelles, CF;Ortiz, MI
在 1% 福尔马林试验中评估了 K+ 通道可能参与白藜芦醇诱导的抗伤害作用。在测试的第二阶段，局部施用白藜芦醇产生剂量依赖性的镇痛作用。白藜芦醇产生的镇痛作用是由于其在对侧爪子中的施用不活跃而产生的局部作用。用格列本脲、甲苯磺丁脲或格列吡嗪（ATP 敏感的 K+ 通道抑制剂）对受伤的爪子进行局部预处理并不能改变白藜芦醇引起的镇痛作用。相反，charybdotoxin 和 apamin（分别为大电导 Ca2+ 和小电导 Ca2+ 激活 K+ 通道阻滞剂）、4-氨基吡啶或四乙铵（电压依赖性 K+ 通道抑制剂）剂量依赖性地阻止白藜芦醇诱导的镇痛作用。局部外周给予格列本脲，但不显着降低外周吗啡产生的镇痛作用（阳性对照）。通过对迈步、翻正、角膜和耳廓反射的评估显示，在最高有效剂量下，所使用的药物均不会引起行为副作用。此外，当单独给药时，没有一种抑制剂能够改变 1% 福尔马林诱导的伤害性行为。结果表明，白藜芦醇打开大电导和小电导 Ca2+ 激活的 K+ 通道，但不打开 ATP 敏感的 K+ 通道，以便在福尔马林试验中产生其外周镇痛作用。还提出了电压依赖性 K+ 通道的参与，但由于使用了非选择性抑制剂，因此数据有待进一步确认。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
The possible participation of K+ channels in the antinociceptive action induced by resveratrol was assessed in the 1% formalin test. Local administration of resveratrol produced a dose-dependent antinociception in the second phase of the test. The antinociception produced by resveratrol was due to a local action as its administration in the contralateral paw was not active. Local pretreatment of the injured paw with glibenclamide, tolbutamide or glipizide (ATP-sensitive K+ channel inhibitors) did not modify resveratrol-induced antinociception. In contrast, charybdotoxin and apamin (large and small conductance Ca2+ activated-K+ channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K+ channel inhibitors) dose-dependently prevented resveratrol-induced antinociception. Local peripheral administration of glibenclamide, but not charybdotoxin or apamin, significantly reduced the antinociceptive effect produced by peripheral morphine (positive control). At the highest effective doses, none of the drugs used induced behavioral side effects as revealed by the evaluation of stepping, righting, corneal and pinna reflexes. In addition, when given alone, none of the inhibitors modified the nociceptive behavior induced by 1% formalin. The results suggest that resveratrol opens large and small conductance Ca2+-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since non-selective inhibitors were used the data awaits further confirmation. (C) 2002 Elsevier Science Ltd. All rights reserved.