Involvement of chloride channel coupled GABA_C receptors in the peripheral antinociceptive effect induced by GABA_C receptor agonist cis-4-aminocrotonic acid

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• 作者：Glá ; ucia Maria Lopes Reis ; Igor Dimitri Gama Duarte
• 关键词：cis-4-aminocrotonic acid ; CACA ; K⁺ channel ; Cl⁻ ; channel ; Peripheral antinociception ; Picrotoxin ; TPMPA
• 刊名：Life Sciences
• 出版年：2007
• 出版时间：13 March 2007
• 年：2007
• 卷：80
• 期：14
• 页码：1268-1273
• 全文大小：333 K

文摘

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 μg) of prostaglandin E₂ (PGE₂). CACA administered locally into the right hindpaw (25, 50 and 100 μg/paw) elicited a dose-dependent antinociceptive 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 μg/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by CACA (100 μg), suggesting a specific effect. This effect was reversed by the chloride channel coupled receptor blocker picrotoxin (0.8 μg/paw). Glibenclamide (160 μg) and tolbutamide (320 μg), blockers of ATP-sensitive potassium channels, charybdotoxin (2 μg), a large-conductance potassium channel blocker, dequalinium (50 μg), a small-conductance potassium channel blocker, and cesium (500 μg), a non-specific 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.