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Int Arch Allergy Immunol. 2010;152(3):295-300. doi: 10.1159/000283042. Epub 2010 Feb 12.

The cannabinoid receptor agonist WIN 55,212-2 inhibits antigen-induced plasma extravasation in guinea pig airways.

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1
Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan.

Abstract

BACKGROUND:

Although neurogenic inflammation of the airways via activation of C-fibers is thought to be important in the pathogenesis of asthma, the mechanisms regulating C-fiber activity remain uncertain.

OBJECTIVE:

The influence of a cannabinoid receptor agonist, WIN 55,212-2, on C-fiber activation in guinea pig airways was investigated, as was the mechanism by which cannabinoids regulate antigen-induced airway inflammation.

METHODS:

The inhibitory effect of WIN 55,212-2 on antigen-induced plasma extravasation was assessed in guinea pig tracheal tissues by photometric measurement of extravasated Evans blue dye after extraction with formamide.

RESULTS:

Pretreatment with WIN 55,212-2 (0.001, 0.01 or 0.1 mg/kg) significantly and dose-dependently reduced tracheal plasma extravasation induced by inhaling a 5% ovalbumin solution for 2 min after pretreatment with a neutral endopeptidedase inhibitor (phosphoramidon at 2.5 mg/kg i.v.). A cannabinoid CB2 receptor antagonist (SR144528) blunted the inhibitory effect of WIN 55,212-2, while a cannabinoid CB1 antagonist (SR141716A) did not. Pretreatment with a neurokinin-1 receptor antagonist (FK888) significantly reduced ovalbumin-induced extravasation of Evans blue dye. Pretreatment with the combination of WIN 55,212-2 and FK888 reduced antigen-induced plasma extravasation more markedly than FK888 alone.

CONCLUSIONS:

These findings suggest that WIN 55,212-2 inhibits C-fiber activation via the cannabinoid CB2 receptor and thus suppresses antigen-induced inflammation in guinea pig airways.

PMID:
20150748
DOI:
10.1159/000283042
[Indexed for MEDLINE]

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