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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.
J Biol Chem 2005; 280(18):18488-97JB

Abstract

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.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15749716

Citation

Oka, Saori, et al. "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." The Journal of Biological Chemistry, vol. 280, no. 18, 2005, pp. 18488-97.
Oka S, Yanagimoto S, Ikeda S, et al. 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. J Biol Chem. 2005;280(18):18488-97.
Oka, S., Yanagimoto, S., Ikeda, S., Gokoh, M., Kishimoto, S., Waku, K., ... Sugiura, T. (2005). 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. The Journal of Biological Chemistry, 280(18), pp. 18488-97.
Oka S, et al. 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. J Biol Chem. 2005 May 6;280(18):18488-97. PubMed PMID: 15749716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Oka,Saori, AU - Yanagimoto,Shin, AU - Ikeda,Shinobu, AU - Gokoh,Maiko, AU - Kishimoto,Seishi, AU - Waku,Keizo, AU - Ishima,Yoshio, AU - Sugiura,Takayuki, Y1 - 2005/03/04/ PY - 2005/3/8/pubmed PY - 2005/9/3/medline PY - 2005/3/8/entrez SP - 18488 EP - 97 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 18 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15749716/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_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15749716 DB - PRIME DP - Unbound Medicine ER -