2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors. To date, two types of cannabinoid receptors (CB
1 and CB
2) have been identified. The CB
1 receptor is assumed to be involved in the attenuation of synaptic transmission. On the other hand, the physiological roles of the CB
2 receptor, which is abundantly expressed in several types of inflammatory cells and immunocompetent cells, have not yet been fully elucidated. Recently, we investigated in detail possible physiological roles of the CB
2 receptor and 2-arachidonoylglycerol in inflammation. We found that 2-arachidonoylglycerol induces the activation of p42/44 and p38 mitogen-activated protein kinases and c-Jun N-terminal kinase; actin rearrangement and morphological changes; augmented production of chemokines in HL-60 cells; and the migration of HL-60 cells differentiated into macrophage-like cells, human monocytes, natural killer cells, and eosinophils. We also found that the level of 2-arachidonoylglycerol in mouse ear is markedly elevated following treatment with 12-
O-tetradecanoylphorbol 13-acetate, which induces acute inflammation. Notably, the inflammation induced by 12-
O-tetradecanoylphorbol 13-acetate was blocked by treatment with SR144528, a CB
2-receptor antagonist. Similar results were obtained with an allergic inflammation model in mice. These results strongly suggest that 2-arachidonoylglycerol plays essential roles in the stimulation of various inflammatory reactions in vivo.
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