Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in the peripheral antinociception of melatonin
Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in the peripheral antinociception of melatonin
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DOI：
10.1016/j.ejphar.2008.07.068
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发表时间：
2008-10-31
影响因子：
5
通讯作者：
Mixcoatl-Zecuatl, Teresa
中科院分区：
文献类型：
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作者：
Hernandez-Pacheco, Alfonso;Ivonne Araiza-Saldana, Claudia;Mixcoatl-Zecuatl, Teresa
在福尔马林实验的第二阶段，评估了一氧化氮(NO)-环GMP-蛋白激酶G(PKG)-K+通道通路在褪黑素诱导的局部抗伤害效应中的可能参与。在福尔马林试验的两个阶段，大鼠局部外周注射褪黑素(150-600微克/爪)均产生剂量相关的抗伤害效应。此外，用N-G-L-硝基精氨酸甲酯(L-NAME，NO合成抑制剂，10-100mU/PAW)、1H-(1，2，4)-恶二唑(4，2-a)喹恶啉-1-酮(ODQ，鸟苷酸环化酶抑制剂，5-50mU/PAW)、(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‘，-吡咯并[3，4-I][1，6]苯并重氮-10-羧酸甲酯(KT-5823，特异性PKG抑制剂，50-500毫克/爪)，格列本脲(三磷酸腺苷敏感钾通道阻滞剂，5-50微克/爪)，阿帕明(小电导钙激活钾通道阻滞剂，0.1-1微克/爪)或白藻毒素(大、中电导钙激活钾通道阻滞剂，0.03-0.3毫克/爪)，但不包括N-G-D-硝基-精氨酸甲酯(D-NAME，L的非活性异构体100微克/爪)或赋形剂，显著阻止褪黑素(300微克/爪)诱导的抗伤害感受。数据表明，在测试的第二阶段，褪黑素诱导的局部外周抗伤害性感觉可能是由于激活了NO-环状GMP-PKG-ATP敏感和钙激活的K+通道。(C)2008爱思唯尔B.V.保留所有权利。
The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG)-K+ channel pathway on melatonin-induced local antinociception was assessed during the second phase of the formalin test. The local peripheral ipsilateral, but not contralateral, administration of melatonin (150-600 mu g/paw) produced a dose-related antinociception during both phases of the formalin test in rats. Moreover, local pretreatment with N-G-L-nitro-arginine methyl ester (L-NAME, NO synthesis inhibitor, 10-100 mu g/paw), 1H-(1,2,4)-oxadiazolo (4,2-a)quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor, 5-50 mu g/paw), (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, 50-500 ng/paw), glibenclamide (ATP-sensitive K+ channel blocker, 5-50 mu g/paw), apamin (small-conductance Ca2+- activated K+ channel blocker, 0.1-1 mu g/paw) or charybdotoxin (large- and intermediate-conductance Ca2+- activated K+ channel blocker, 0.03-0.3 mu g/paw), but not N-G-D-nitro-arginine methyl ester (D-NAME, inactive isomer Of L-NAME, 100 mu g/paw) or vehicle, significantly prevented melatonin (300 mu g/paw)-induced antinociception. Data suggest that melatonin-induced local peripheral antinociception during the second phase of the test could be due to activation of the NO-cyclic GMP-PKG-ATP-sensitive and Ca2+-activated K+ channels pathway. (C) 2008 Elsevier B.V. All rights reserved.