Effects of cannabinoid receptor agonists on immunologically induced histamine release from rat peritoneal mast cells

Alaster H. Y. Lau, Sharron S. M. Chow

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Immunologic activation of mast cells through the cross-linking of high affinity IgE receptors results in the release of inflammatory mediators which are important in the pathogenesis of allergic reactions. Early studies investigating the effects of palmitoylethanolamide on animal models of inflammation and on rat mast cells led to the hypothesis that endogenous cannabinoids might act as local autacoids which suppressed inflammation by reducing the activation of mast cells. However, more recent studies produced contradicting results. In order to evaluate if cannabinoid receptors are present in mast cells, we studied the effects of endocannabinoids (anandamide and palmitoylethanolamide) and synthetic cannabimimetics (CP 55,940, WIN 55,212-2 and HU-210) on histamine release from rat peritoneal mast cells. When incubated with mast cells alone, only anandamide could induce significant level of histamine release at concentrations higher than 10(-6) M. When mast cells were activated with anti-IgE, the histamine release induced was not affected by anandamide, palmitoylethanolamide and CP 55,940. In contrast, both WIN 55,212-2 and HU-210 enhanced anti-IgE-induced histamine release at 10(-5) M and preincubation did not increase the potency. The histamine releasing action of anandamide and the enhancing effects of WIN 55,212-2 and HU-210 on anti-IgE-induced histamine release were not reduced by the cannabinoid receptor antagonists, AM 281 and AM 630. In conclusion, the present study does not support the hypothesis that cannabinoids suppress mast cell activation. Instead, some of the cannabinoid receptor-directed ligands tested enhanced mast cell activation. However, the high concentrations required and the failure of cannabinoid receptor antagonists to reverse such effects also question the existence of functional cannabinoid receptors in mast cells.

Original languageEnglish
Pages (from-to)229-235
Number of pages7
JournalEuropean Journal of Pharmacology
Volume464
Issue number2-3
DOIs
Publication statusPublished - 19 Mar 2003
Externally publishedYes

Keywords

  • Cannabinoid receptor
  • Mast cell
  • Histamine release, anti-IgE-induced
  • Anandamide
  • Palmitoylethanolamide
  • WIN 55,512-2

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