Involvement of chloride channel coupled GABAC receptors in the peripheral antinociceptive effect induced by GABAC receptor agonist cis-4-aminocrotonic acid
Involvement of chloride channel coupled GABAC receptors in the peripheral antinociceptive effect induced by GABAC receptor agonist cis-4-aminocrotonic acid
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氯通道偶联 GABAC 受体参与 GABAC 受体激动剂顺式-4-氨基巴豆酸诱导的外周抗痛觉效应
DOI：
10.1016/j.lfs.2006.12.015
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发表时间：
2007-03-13
期刊：
影响因子：
6.1
通讯作者：
Gama Duarte, Igor Dimitri
中科院分区：
文献类型：
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作者：
Lopes Reis, Glaucia Maria;Gama Duarte, Igor Dimitri
我们使用爪压试验研究了氯离子通道阻滞剂和钾通道阻滞剂对 GABA(C) 受体激动剂 CACA（顺-4-氨基巴豆酸）诱导的镇痛作用的影响，其中足底注射（2 μg）前列腺素 E-2 (PGE(2)) 可增加疼痛敏感性。将CACA局部注射到右后爪（25、50和100μg/爪）引起剂量依赖性氨基感受效应，该效应被证明是局部的，因为只有较高剂量注射到对侧爪时才会产生效应。 GABA(C)受体拮抗剂（1,2,5,6四氢吡啶-4-基）甲基次膦酸（TPMPA；5、10和20μg/爪）以剂量依赖性方式拮抗CACA（100μg）诱导的外周镇痛作用，表明具有特定作用。这种效应被氯离子通道偶联受体阻断剂印防己毒素（0.8μg/爪）逆转。 ATP敏感钾通道阻滞剂格列本脲（160μg）和甲苯磺丁脲（320μg）、大电导钾通道阻滞剂卡雷布毒素（2μg）、小电导钾通道阻滞剂地喹啉（50μg）和非特异性钾通道阻滞剂铯（500μg）没有改变CACA诱导的外周镇痛作用。这项研究提供的证据表明，外周 GABA(C) 受体的激活会诱导镇痛，这种作用是由氯离子通道偶联的 GABA(C) 受体激活引起的，而钾通道似乎不参与其中。 (c) 2007 Elsevier Inc. 保留所有权利。
We investigated the effect of chloride and potassium channel blockers on the antinociception induced by GABA(C) receptor agonist CACA (cis-4-aminocrotonic acid) using the paw pressure test, in which pain sensitivity was increased by an intraplantar injection (2 mu g) of prostaglandin E-2 (PGE(2)). CACA administered locally into the right hindpaw (25, 50 and 100 mu g/paw) elicited a dose-dependent aminociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The GABA(C) receptor antagonist (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA; 5, 10 and 20 mu g/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by CACA (100 mu g), suggesting a specific effect. This effect was reversed by the chloride channel coupled receptor blocker picrotoxin (0.8 mu g/paw). Glibenclamide (160 mu g) and tolbutamide (320 mu g), blockers of ATP-sensitive potassium channels, charybdotoxin (2 mu g), a large-conductance potassium channel blocker, dequalinium (50 mu g), a small-conductance potassium channel blocker, and cesium (500 mu g), a nonspecific potassium channel blocker did not modify the peripheral antinociception induced by CACA. This study provides evidence that activation of GABA(C) receptors in the periphery induces antinociception, that this effect results from the activation of chloride channel coupled GABA(C) receptors and that potassium channels appear not to be involved. (c) 2007 Elsevier Inc. All rights reserved.