The Cannabinoid Receptor Agonist WIN 55,212-2 Inhibits Antigen-Induced Plasma Extravasation in Guinea Pig Airways

• Published in: International archives of allergy and immunology Vol. 152; no. 3; pp. 295 - 300
• Main Authors: Fukuda, Hironobu, Abe, Toshio, Yoshihara, Shigemi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2010; S. Karger AG
• Subjects: Animals; Antigens - administration & dosage; Antigens - immunology; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; Biological and medical sciences; Camphanes - pharmacology; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Capillary Permeability - drug effects; Capillary Permeability - immunology; Dipeptides - pharmacology; Drugs; Evans Blue - administration & dosage; Evans Blue - metabolism; Extravasation of Diagnostic and Therapeutic Materials - immunology; Extravasation of Diagnostic and Therapeutic Materials - metabolism; Extravasation of Diagnostic and Therapeutic Materials - prevention & control; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Guinea Pigs; Immunization; Immunopathology; Indoles - pharmacology; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Male; Medical sciences; Morpholines - pharmacology; Morpholines - therapeutic use; Naphthalenes - pharmacology; Naphthalenes - therapeutic use; Neurokinin-1 Receptor Antagonists; Original Paper; Ovalbumin - administration & dosage; Ovalbumin - immunology; Piperidines - pharmacology; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Respiratory Hypersensitivity - drug therapy; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - metabolism; Respiratory system; Rimonabant; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Trachea - blood supply; Trachea - drug effects; Trachea - metabolism; Plasma extravasation; Guinea pig; WIN 55,212-2; C-fibers; Cannabinoid; Antigen challenge; Airway; Agonist; Fiber; Respiratory system; Blood plasma; Respiratory tract; Immunology; Extravasation; Cannabinoid receptor; Immunopathology; Nutrition; Rodentia; Feeding; Antigen; Vertebrata; Mammalia; Diet; Animal; Inhibitor
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000283042

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.