Evidence for the involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation in mouse ear.
2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors. Two types of cannabinoid receptors have been identified to date. The CB1 receptor is abundantly expressed in the brain, and assumed to be involved in the attenuation of neurotransmission. On the other hand, the physiological roles of the CB2 receptor, mainly expressed in several types of inflammatory cells and immunocompetent cells, have not yet been fully elucidated. In this study, we investigated possible pathophysiological roles of the CB2 receptor and 2-arachidonoylglycerol in acute inflammation in mouse ear induced by the topical application of 12-O-tetradecanoylphorbol-13-acetate. We found that the amount of 2-arachidonoylglycerol was markedly augmented in inflamed mouse ear. In contrast, the amount of anandamide, another endogenous cannabinoid receptor ligand, did not change markedly. Importantly, 12-O-tetradecanoylphorbol-13-acetate-induced ear swelling was blocked by treatment with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the swelling. On the other hand, the application of AM251, a CB1 receptor antagonist, exerted only a weak suppressive effect. The application of SR144528 also reduced the 12-O-tetradecanoylphorbol-13-acetate-induced production of leukotriene B(4) and the infiltration of neutrophils in the mouse ear. Interestingly, the application of 2-arachidonoylglycerol to the mouse ear evoked swelling, which was abolished by treatment with SR144528. Nitric oxide was suggested to be involved in the ear swelling induced by 2-arachidonoylglycerol. These results suggest that the CB2 receptor and 2-arachidonoylglycerol play crucial stimulative roles during the course of inflammatory reactions.
Oka
Saori
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
Yanagimoto
Shin
S
Ikeda
Shinobu
S
Gokoh
Maiko
M
Kishimoto
Seishi
S
Waku
Keizo
K
Ishima
Yoshio
Y
Sugiura
Takayuki
T
D000287:Administration, Topical; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001892:Camphanes / Q000494:pharmacology / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000502:physiology; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D001095:Arachidonic Acids; D001892:Camphanes; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D008024:Ligands; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C094503:glyceryl 2-arachidonate; D013755:Tetradecanoylphorbol Acetate