The Cannabinoid Receptor Agonist WIN 55212-2 Inhibits Neurogenic Inflammations in Airway Tissues

• Published in: Journal of Pharmacological Sciences Vol. 98; no. 1; pp. 77 - 82
• Main Authors: Yoshihara, Shigemi, Morimoto, Hiroshi, Ohori, Makoto, Yamada, Yumi, Abe, Toshio, Arisaka, Osamu
• Format: Journal Article
• Language: English; Japanese
• Published: Japan Elsevier B.V 2005; The Japanese Pharmacological Society; Elsevier
• Subjects: Animals; Benzoxazines; Bronchoconstriction - drug effects; Bronchoconstriction - physiology; bronchoconstrictoin; C-fiber; cannabinoid; Guinea Pigs; Male; Maxi-K+ channel; Morpholines - pharmacology; Naphthalenes - pharmacology; Nerve Fibers, Unmyelinated - drug effects; Nerve Fibers, Unmyelinated - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; plasma extravasation; Rats; Rats, Wistar; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - physiology; Trachea - drug effects; Trachea - physiology; C-fiber; bronchoconstrictoin; Maxi-K+ channel; cannabinoid; plasma extravasation
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.fp0050171

We examined the effects of a cannabinoid receptor agonist, (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-merpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone (WIN 55212-2), on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). WIN 55212-2 significantly inhibited capsaicin-induced guinea pig bronchoconstriction, but not the neurokinin A-induced reaction. Intravenous injection of WIN 55212-2 also blocked cigarette smoke-induced rat tracheal plasma extravasation. However, substance P-induced rat tracheal plasma extravasation was not affected by the administration of WIN 55212-2. A cannabinoid CB2 receptor antagonist, {N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide} (SR 144528) reduced the inhibitory effects of WIN 55212-2, but not a cannabinoid CB1 antagonist, [N-(pipe-ridin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride] (SR 141716A). A Maxi-K+ channel opener, 1-(2′-hydroxy-5′-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimidazolone (NS 1619), specifically inhibited capsaicin-induced guinea pig bronchoconstriction and cigarette smoke-induced rat tracheal plasma extravasation. These findings suggest that WIN 55212-2 inhibits the activation of C-fibers via cannabinoid CB2 receptors and Maxi-K+ channels and reduces airway neurogenic inflammatory reactions in vivo.