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Review
. 2007 Nov;152(5):594-601.
doi: 10.1038/sj.bjp.0707379. Epub 2007 Jul 9.

The contribution of cyclooxygenase-2 to endocannabinoid metabolism and action

C J Fowler  1
Affiliations
Review

The contribution of cyclooxygenase-2 to endocannabinoid metabolism and action

C J Fowler. Br J Pharmacol. 2007 Nov.

Abstract

The development of sensitive analytical methods for measurement of endocannabinoids, their metabolites, and related lipids, has underlined the complexity of the endocannabinoid system. A case can be made for an 'endocannabinoid soup' (akin to the inflammatory soup) whereby the net effect of a pathological state and/or a pharmacological intervention on this system is the result not only of changes in endocannabinoid levels but also of their metabolites and related compounds that affect their function. With respect to the metabolism of anandamide and 2-arachidonoylglycerol, the main hydrolytic enzymes involved are fatty acid amide hydrolase and monoacylglycerol lipase. However, other pathways can come into play when these are blocked. Cyclooxygenase-2 derived metabolites of anandamide and 2-arachidonoylglycerol have a number of properties, including effects upon cell viability, contraction of the cat iris sphincter (an effect mediated by a novel receptor), mobilization of calcium and modulation of synaptic transmission. Nonsteroidal anti-inflammatory agents, whose primary mode of action is the inhibition of cyclooxygenase, can also interact with the endocannabinoid system both in vitro and in vivo. Other enzymes, such as the lipoxygenase and cytochrome P450 oxidative enzymes, can also metabolize endocannabinoids and produce biologically active compounds. It is concluded that sensitive analytical methods, which allow for measurement of endocannabinoids and related lipids, should provide vital information as to the importance of these alternative metabolic pathways when the primary hydrolytic endocannabinoid metabolizing enzymes are inhibited.

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Figures

Figure 1
Figure 1
(a) Schematic representation of the roles of FAAH, MGL and COX-2 in the metabolism of AEA, 2-AG and the related N-acylethanolamines OEA and PEA. The endocannabinoids are poor substrates for COX-1 compared to COX-2, at least in cell-free systems. Further metabolism of the oleic acid (OA), palmitic acid (PA) and AA has not been shown in the figure, for reasons of simplicity. (b) Structures of AEA, 2-OG and representative COX-2 metabolites (PGE2-EA and PGE2-GE). 2-AG, 2-arachidonoylglycerol; AA, arachidonic acid; AEA, anandamide; COX, cyclooxygenase; FAAH, fatty acid amide hydrolase; MGL, monoacylglycerol lipase; OA, oleic acid; OEA, oleoylethanolamide; PA, palmitic acid; PEA, palmitoylethanolamide; PG-EA, prostaglandin ethanolamides (‘prostamides'); PG-GE, prostaglandin glyceryl esters.
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References

    1. Anikwue R, Huffman JW, Martin ZL, Welch SP. Decrease in efficacy and potency of nonsteroidal anti-inflammatory drugs by chronic Δ9-tetrahydrocannabinol administration. J Pharmacol Exp Ther. 2002;303:340–346. - PubMed
    1. Ates M, Hamza M, Seidel K, Kotalla CE, Ledent C, Gühring H. Intrathecally applied flurbiprofen produces an endocannabinoid-dependent antinociception in the rat formalin test. Eur J Neurosci. 2003;17:597–604. - PubMed
    1. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee M-H, Vogel Z, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998;353:23–31. - PubMed
    1. Berger C, Schmid PC, Schabitz W-R, Wolf M, Schwab S, Schmid HHO. Massive accumulation of N-acylethanolamines after stroke. Cell signalling in acute cerebral ischemia. J Neurochem. 2004;88:1159–1167. - PubMed
    1. Berglund BA, Boring DL, Howlett AC. Investigation of structural analogs of prostaglandin amides for binding to and activation of CB1 and CB2 cannabinoid receptors in rat brain and human tonsils. Adv Exp Med Biol. 1999;469:527–533. - PubMed

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