Pharmacological evidence for the activation of K+ channels by diclofenac
Pharmacological evidence for the activation of K+ channels by diclofenac
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DOI：
10.1016/s0014-2999(02)01288-8
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发表时间：
2002-03-01
影响因子：
5
通讯作者：
Granados-Soto, V
中科院分区：
文献类型：
--
作者：
Ortiz, MI;Torres-López, JE;Granados-Soto, V
福尔马林实验观察K+通道在双氯芬酸抗伤害作用中的作用。双氯芬酸局部给药由于局部作用而产生剂量依赖的抗伤害效应，因为对侧爪给药无效。用三磷酸腺苷敏感性钾通道阻断剂格列本脲和甲苯丁胺、大电导和小电导钙激活钾通道阻断剂夏洛多毒素和阿帕明、电压依赖性钾通道阻滞剂4-氨基吡啶或四乙基铵对损伤足进行预处理，可阻断双氯芬酸的抗伤害性作用。单独给予K+通道抑制剂不能改变福尔马林诱导的伤害性行为。匹那地尔(一种对ATP敏感的K+通道开放剂)也产生抗伤害性作用，但格列本脲可阻断这种作用。吗啡(阳性对照)的外周抗伤害性作用可被格列本脲和4-氨基吡啶阻断，但不能被河豚毒素或阿帕明阻断。结果提示，双氯芬酸的外周抗伤害性作用可能是通过激活多种K+通道，引起初级传入神经末梢超极化所致。(C)2002 Elsevier Science B.V.保留所有权利。
The involvement of K+ channels in the antinociceptive action of diclofenac was assessed in the formalin test. Local administration of diclofenac produced a dose-dependent antinociceptive effect due to a local action because drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with glibenclamide and tolbutamide (ATP-sensitive K+ channel inhibitors), charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K+ channel inhibitors) prevented diclofenac-induced antinociception. Given alone, K+ channel inhibitors did not modify formalin-induced nociceptive behavior. Pinacidil (an ATP-sensitive K+ channel opener) also produced antinociception which was blocked by glibenclamide. The peripheral antinociceptive effect of morphine (positive control) was blocked by glibenclamide and 4-aminopyridine but not by charybdotoxin or apamin. The results suggest that the peripheral antinociceptive effect of diclofenac may result from the activation of several types of K+ channels, which may cause hyperpolarization of peripheral terminals of primary afferents. (C) 2002 Elsevier Science B.V. All rights reserved.