Participation of the nitric oxide-cyclic GMP-ATP-sensitive K+ channel pathway in the antinociceptive action of ketorolac
Participation of the nitric oxide-cyclic GMP-ATP-sensitive K+ channel pathway in the antinociceptive action of ketorolac
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DOI：
10.1016/s0014-2999(01)01206-7
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发表时间：
2001-08-24
影响因子：
5
通讯作者：
Granados-Soto, V
中科院分区：
文献类型：
--
作者：
Lázaro-Ibáñez, GG;Torres-López, JE;Granados-Soto, V
采用大鼠福尔马林试验评估一氧化氮（NO）、环GMP和atp敏感的K+通道参与酮乐酸的抗伤性作用。由于对侧足部给药无效，在福尔马林损伤的足部局部给药酮咯酸产生了剂量依赖性的抗痛感作用。用n- g - l -硝基精氨酸甲酯（L-NAME，一种NO合成抑制剂）、1H-(1,2,4)-恶二唑（4,2-a）喹诺沙林-1-酮（ODQ，一种可溶性关酰环化酶抑制剂）或格列本脲（一种atp敏感的K+通道阻滞剂）预处理伤爪，可阻止酮酸诱导的抗痛反应。然而，用生理盐水或n - g - d -硝基精氨酸甲酯（D-NAME）预处理并没有阻断抗炎反应。局部给药s -亚硝基-n -乙酰青霉胺（SNAP， NO供体）本身无活性，但增加了酮罗拉酸的作用。目前的研究结果表明，酮洛酸的抗伤感受作用涉及激活no -环GMP通路，随后在外周水平打开atp敏感的K+通道。(C) 2001年Elsevier Science B.V.出版
The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K+ channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N-G-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K+ channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N-G-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K+ channels at the peripheral level. (C) 2001 Published by Elsevier Science B.V.