Prostaglandin E 2 glycerol ester, an endogenous COX-2 metabolite of 2-arachidonoylglycerol, induces hyperalgesia and modulates NFκB activity

S. Shu Jung Hu, H. B. Bradshaw, J. S.C. Chen, B. Tan, J. Michael Walker

研究成果: Article同行評審

130 引文 斯高帕斯(Scopus)

摘要

Background and purpose: Recombinant cyclooxygenase-2 (COX-2) oxygenates 2-arachidonoylglycerol (2-AG) in vitro. We examined whether prostaglandin E 2 glycerol ester (PGE 2-G), a COX-2 metabolite of 2-AG, occurs endogenously and affects nociception and immune responses. Experimental approach: Using mass spectrometric techniques, we examined whether PGE 2-G occurs in vivo and if its levels are altered by inhibition of COX-2, monoacylglycerol (MAG) lipase or inflammation induced by carrageenan. We also examined the effects of PGE 2-G on nociception in rats and NFκB activity in RAW264.7 cells. Key results: PGE 2-G occurs endogenously in rat. Its levels were decreased by inhibition of COX-2 and MAG lipase but were unaffected by carrageenan. Intraplantar administration of PGE 2-G induced mechanical allodynia and thermal hyperalgesia. In RAW264.7 cells, PGE 2-G and PGE 2 produced similar, dose-related changes in NFκB activity. PGE 2-G was quickly metabolized into PGE 2. While the effects of PGE 2 on thermal hyperalgesia and NFκB activity were completely blocked by a cocktail of antagonists for prostanoid receptors, the same cocktail of antagonists only partially antagonized the actions of PGE 2-G. Conclusions and implications: Thermal hyperalgesia and immunomodulation induced by PGE 2-G were only partially mediated by PGE 2, which is formed by metabolism of PGE 2-G. PGE 2-G may function through a unique receptor previously postulated to mediate its effects. Taken together, these findings demonstrate that 2-AG is oxygenated in vivo by COX-2 producing PGE 2-G, which plays a role in pain and immunomodulation. COX-2 could act as an enzymatic switch by converting 2-AG from an antinociceptive mediator to a pro-nociceptive prostanoid.

原文English
頁(從 - 到)1538-1549
頁數12
期刊British Journal of Pharmacology
153
發行號7
DOIs
出版狀態Published - 2008 4月

All Science Journal Classification (ASJC) codes

  • 藥理

指紋

深入研究「Prostaglandin E 2 glycerol ester, an endogenous COX-2 metabolite of 2-arachidonoylglycerol, induces hyperalgesia and modulates NFκB activity」主題。共同形成了獨特的指紋。

引用此