Involvement of cannabinoid CB2 receptors in the IgE-mediated triphasic cutaneous reaction in mice.
Involvement of cannabinoid CB2 receptors in the IgE-mediated cutaneous reaction was investigated. Epicutaneous challenge with 2,4-dinitrofluorobenzene caused a triphasic swelling in the ear of BALB/c and C57BL/6 mice passively sensitized with anti-dinitrophenol IgE. Peak responses of the ear swelling appeared at 1 h, 24 h, and 8 days after the challenge in both strains of mice. In contrast, cannabinoid CB2 receptor-deficient mice failed to exhibit the obvious triphasic ear swelling observed in wild-type mice. Oral administration of cannabinoid CB2 receptor antagonist/inverse agonists [N-(benzo[1,3]dioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxamide] (JTE-907) and {N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2yl]5-(4-chloro-3-methyl-phenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide} (SR144528) at doses of 0.1-10 mg/kg significantly and dose-dependently suppressed all three phases of ear swelling in BALB/c mice. Interestingly, epicutaneous treatment with an ether-linked analogue of endogenous cannabinoids, 2-arachidonoylglycerol, caused an ear swelling that could be detected at 1 h, 24 h, and 8 days after treatment of both BALB/c and C57BL/6 mice. These results suggest that cannabinoid CB2 receptors are involved in induction of the triphasic cutaneous reaction mediated by IgE, and that cannabinoid CB2 receptor antagonist/inverse agonists may serve as anti-allergic agents in the treatment of allergic dermatitis.
Ueda
Yoshifumi
Y
Japan Tobacco Inc., Central Pharmaceutical Research Institute, Takatsuki, Osaka, 569-1125, Japan. yoshifumi.ueda@ims.jti.co.jp
Miyagawa
Naoki
N
Wakitani
Korekiyo
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism*; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011720:Pyrazoles / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001892:Camphanes; D004149:Dioxoles; C422645:JTE 907; D008024:Ligands; D011720:Pyrazoles; D015363:Quinolones; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D007073:Immunoglobulin E; D004139:Dinitrofluorobenzene