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

Abstract

AIMS:

Recently, we demonstrated that peripheral antinociception induced by δ 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, 2μg). Nociceptive thresholds to pressure (grams) were measured using an algesimetric apparatus 3h 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 50μg/paw) and the cannabinoid agonist CB2 PEA (5, 10 and 20μg/paw) decreased the PGE2-induced hyperalgesia in a dose-dependent manner. The possibility of the higher doses of anandamide (50μg) and PEA (20μg) 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 32μg).

SIGNIFICANCE:

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

• Authors: Thiago Roberto Lima Romero, Daniela da Fonseca Pacheco, Igor Dimitri Gama Duarte
• Journal: Life sciences (Life Sci) Vol. 92 Issue 14-16 Pg. 815-20 (May 02 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23123446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Amides
• Arachidonic Acids
• Calcium Channel Blockers
• Cannabinoid Receptor Agonists
• Chloride Channels
• Endocannabinoids
• Ethanolamines
• Indoles
• Palmitic Acids
• Piperidines
• Polyunsaturated Alkamides
• Pyrazoles
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• AM 251
• Niflumic Acid
• palmidrol
• Dinoprostone
• iodopravadoline
• anandamide

Topics

• Amides
• Analysis of Variance
• Animals
• Arachidonic Acids (administration & dosage, pharmacology)
• Calcium Channel Blockers (administration & dosage, pharmacology)
• Cannabinoid Receptor Agonists (administration & dosage, pharmacology)
• Chloride Channels (drug effects, metabolism)
• Dinoprostone
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Endocannabinoids (administration & dosage, pharmacology)
• Ethanolamines (administration & dosage, pharmacology)
• Hyperalgesia (drug therapy)
• Indoles (pharmacology)
• Male
• Niflumic Acid (administration & dosage, pharmacology)
• Palmitic Acids (administration & dosage, pharmacology)
• Piperidines (pharmacology)
• Polyunsaturated Alkamides (administration & dosage, pharmacology)
• Pyrazoles (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Cannabinoid, CB1 (agonists, metabolism)
• Receptor, Cannabinoid, CB2 (agonists, metabolism)