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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

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

Thiago Roberto Lima Romero1, Daniela da Fonseca Pacheco, Igor Dimitri Gama Duarte

  • 1Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270.100, Belo Horizonte, Brazil.

Life Sciences
|November 6, 2012
PubMed
Abstract

Insights

Peripheral antinociception mediated by the CB1 cannabinoid receptor involves calcium-activated chloride channels (CaCCs). This study shows CaCCs are essential for the pain-relieving effects of anandamide, a cannabinoid agonist.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Peripheral antinociception via delta opioid receptors is Ca(2+)-activated Cl(-) channels (CaCCs)-dependent.
  • Opioid and cannabinoid receptors share common signaling pathways.
  • Investigating the link between CaCCs and the endocannabinoid system is warranted.

Purpose of the Study:

  • To determine if CaCCs are involved in the peripheral antinociception induced by cannabinoid receptor activation.
  • To explore the relationship between CaCCs and the endocannabinoid system in pain modulation.

Main Methods:

  • Hyperalgesia was induced in rat paws using prostaglandin E2 (PGE2).
  • Nociceptive thresholds were measured using an algesimetric apparatus.
  • Cannabinoid agonists (anandamide, PEA) and antagonists (AM251, AM630), along with a CaCC blocker (niflumic acid), were administered to assess antinociceptive effects.

Main Results:

  • Both anandamide (CB1 agonist) and PEA (CB2 agonist) dose-dependently reduced PGE2-induced hyperalgesia.
  • Antinociception was specific to peripheral administration and blocked by CB1 and CB2 antagonists.
  • Peripheral antinociception induced by anandamide, but not PEA, was inhibited by the CaCC blocker niflumic acid.

Conclusions:

  • This study provides the first evidence linking CaCCs to peripheral antinociception.
  • CaCCs are crucially involved in the pain-relieving effects mediated by CB1 cannabinoid receptor activation.

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