Involvement of cannabinoid CB(2) receptor-mediated response and efficacy of cannabinoid CB(2) receptor inverse agonist, JTE-907, in cutaneous inflammation in mice.
Involvement of cannabinoid CB(2) receptor and effect of cannabinoid CB(2) receptor antagonist/inverse agonists on cutaneous inflammation were investigated. Mice ears topically exposed to an ether-linked analogue of 2-arachidonoylglycerol (2-AG-E) or selective cannabinoid CB(2) receptor agonist, {4-[4-(1,1-dimethylheptyl)-2,6-dimethoxy-phenyl]-6.6-dimethyl-bicyclo[3.1.1]hept-2-en-2-yl}-methanol (HU-308), had early and late ear swelling (0--24 h and 1--8 days after exposure, respectively). Both types of responses induced by 2-AG-E were significantly suppressed by oral administration of cannabinoid CB(2) 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-2 yl]5-(4-chloro-3-methyl-phenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide}} (SR 144528). In contrast, JTE-907 did not affect arachidonic acid-induced swelling. Orally administered JTE-907 (0.1-10 mg/kg) and SR 144528 (1 mg/kg) also produced significant inhibition of dinitrofluorobenzene-induced ear swelling, with increased cannabinoid CB(2) receptor mRNA expression observed in the inflamed ear. These results suggest that cannabinoid CB(2) receptor is partially involved in local inflammatory responses and cannabinoid CB(2) receptor antagonist/inverse agonist has beneficial effects on ear swelling.
Ueda
Yoshifumi
Y
Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1 Murasaki-cho, Takatsuki, Osaka, 569-1125, Japan. yoshifumi.ueda@ims.jti.co.jp
Miyagawa
Naoki
N
Matsui
Tomoko
T
Kaya
Tetsudo
T
Iwamura
Hiroyuki
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D016718:Arachidonic Acid; D019540:Area Under Curve; D001892:Camphanes / Q000494:pharmacology; D002186:Cannabinoids; D004139:Dinitrofluorobenzene; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D003875:Drug Eruptions / Q000517:prevention & control*; D004431:Ear, External / Q000737:chemistry; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008198:Lymph Nodes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011720:Pyrazoles / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001892:Camphanes; D002186:Cannabinoids; D004149:Dioxoles; C422645:JTE 907; D011720:Pyrazoles; D015363:Quinolones; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D016718:Arachidonic Acid; C402416:HU 308; D004139:Dinitrofluorobenzene; D007213:Indomethacin