Probable involvement of Ca^2 +-activated Cl^? channels (CaCCs) in the activation of CB₁ cannabinoid receptors

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• 作者：Thiago Roberto Lima Romero ; Daniela da Fonseca Pacheco ; Igor Dimitri Gama Duarte ; ^{dimitri@icb.ufmg.br}
• 关键词：Anandamide ; Palmitoylethanolamine ; Niflumic acid ; CaCC ; Peripheral antinociception
• 刊名：Life Sciences
• 出版年：2013
• 出版时间：2 May, 2013
• 年：2013
• 卷：92
• 期：14-16
• 页码：815-820
• 全文大小：2960 K

文摘

Aims

Recently, we demonstrated that peripheral antinociception induced by ¦Ä opioid receptor is dependent of Ca^2 +-activated Cl^? channels (CaCCs). Because opioid and cannabinoid receptors share some common mechanisms of action, our objective was to identify a possible relationship between CaCCs and the endocannabinoid system.

Main methods

To induce hyperalgesia, rat paws were treated with intraplantar prostaglandin E₂ (PGE₂, 2 ¦Ìg). Nociceptive thresholds to pressure (grams) were measured using an algesimetric apparatus 3 h following injection. Probabilities were calculated using ANOVA/Bonferroni's test, and values that were less than 5 % were considered to be statistically significant.

Key findings

Administration of the cannabinoid agonist CB₁ anandamide (12.5, 25 and 50 ¦Ìg/paw) and the cannabinoid agonist CB₂ PEA (5, 10 and 20 ¦Ìg/paw) decreased the PGE₂-induced hyperalgesia in a dose-dependent manner. The possibility of the higher doses of anandamide (50 ¦Ìg) and PEA (20 ¦Ìg) having a central or systemic effect was excluded because the administration of the drug into the contralateral paw did not elicit antinociception in the right paw. As expected, the antinociceptive effects induced by anandamide and PEA were blocked by the CB₁ and CB₂ receptor antagonists AM251 and AM630, respectively. The peripheral antinociception was induced by anandamide but not PEA and was dose-dependently inhibited by the CaCC blocker niflumic acid (8, 16 and 32 ¦Ìg).

Significance

These results provide the first evidence for the involvement of CaCCs in the peripheral antinociception induced by activation of the CB₁ cannabinoid receptor.