M. Yu et al., SYNTHESIS OF PROSTAGLANDIN E-2 ETHANOLAMIDE FROM ANANDAMIDE BY CYCLOOXYGENASE-2, The Journal of biological chemistry, 272(34), 1997, pp. 21181-21186
Because of its structural similarity to polyunsaturated fatty acids, a
nandamide could serve as substrate for enzymes such as lipoxygenases a
nd cyclooxygenases, which metabolize polyunsaturated fatty acids to po
tent bioactive metabolites. Here the ability of recombinant human cycl
ooxygenase-l (hCOX-1) and cyclooxygenase-2 (hCOX-2) to metabolize anan
damide was studied. Baculovirus-expressed and -purified hCOX-2, but no
t hCOX-1, effectively oxygenated anandamide. Reverse phase high pressu
re liquid chromatography analysis of the products derived from 1-C-14-
labeled anandamide showed that the products formed are similar to thos
e formed with arachidonic acid as substrate. The major prostanoid prod
uct derived from anandamide was determined by mass spectrometry to be
prostaglandin E-2 ethanolamide. Incubation of anandamide with lysates
and the intact cell line expressing COX-2 but not that of COX-1 produc
ed prostaglandin E-2 ethanolamide. These results demonstrate the exist
ence of a COX-a-mediated pathway for anandamide metabolism, and the me
tabolites formed represent a novel class of prostaglandins.