Noradrenaline activates the NO/cGMP/ATP-sensitive K⁺ channels pathway to induce peripheral antinociception in rats

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• 作者：Thiago R.L. Romero ^{thiromero@gmail.com} ; Luciana S. Guzzo ^{luguzzo@yahoo.com.br} ; Andrea C. Perez ^{acp@icb.ufmg.br} ; André ; Klein ; Igor D.G. Duarte ; ^{dimitri@icb.ufmg.br}
• 关键词：Noradrenaline ; Nitric oxide ; K+ channels ; Peripheral antinociception
• 刊名：Nitric Oxide
• 出版年：2012
• 期刊代码：181_10898603
• 类别：bio
• 出版时间：31 March, 2012
• 卷：26
• 期：3
• 页码：157-161
• 文件大小：496 K

摘要

Despite the classical peripheral pronociceptive effect of noradrenaline (NA), recently studies showed the involvement of NA in antinociceptive effect under immune system interaction. In addition, the participation of the NO/cGMP/KATP pathway in the peripheral antinociception has been established by our group as the molecular mechanism of another adrenoceptor agonist xylazine. Thus the aim of this study was to obtain pharmacological evidences for the involvement of the NO/cGMP/KATP pathway in the peripheral antinociceptive effect induced by exogenous noradrenaline. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E₂ (2 渭g/paw). All drugs were locally administered into the right hind paw of male Wistar rats. NA (5, 20 and 80 ng/paw) elicited a local inhibition of hyperalgesia. The non-selective NO synthase inhibitor l-NOarg (12, 18 and 24 渭g/paw) antagonized the antinociception effect induced by the highest dose of NA. The soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100 渭g/paw) antagonized the NA-induced effect; and cGMP-phosphodiesterase inhibitor zaprinast (50 渭g/paw) potentiated the antinociceptive effect of NA low dose (5 ng/paw). In addition, the local effect of NA was antagonized by a selective blocker of an ATP-sensitive K⁺ channel, glibenclamide (20, 40 and 80 渭g/paw). On the other hand, the specifically voltage-dependent K⁺ channel blocker, tetraethylammonium (30 渭g/paw), Ca²⁺-activated K⁺ channel blockers of small and large conductance types dequalinium (50 渭g/paw) and paxilline (20 渭g/paw), respectively, were not able to block local antinociceptive effect of NA. The results provide evidences that NA probably induces peripheral antinociceptive effects by activation of the NO/cGMP/KATP pathway.