The cannabinoid receptor agonist WIN 55,212-2 inhibits antigen-induced plasma extravasation in guinea pig airways.
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.
Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan.
Hironobu
H
Fukuda
Toshio
T
Abe
Shigemi
S
Yoshihara
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D004151:Dipeptides / Q000494:pharmacology; D005070:Evans Blue / Q000008:administration & dosage / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D006168:Guinea Pigs; D007114:Immunization; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D000077285:Rimonabant; D014132:Trachea / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*
D000941:Antigens; D048588:Benzoxazines; D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D004151:Dipeptides; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C078949:FK 888; D005070:Evans Blue; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D010047:Ovalbumin; D000077285:Rimonabant