A. Zosmer et al., FORMATION AND METABOLISM OF 14,15-EPOXYEICOSATRIENOIC ACID BY HUMAN REPRODUCTIVE TISSUES, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1258(3), 1995, pp. 234-240
Human granulosa-luteal cells cultured in the presence of arachidonic a
cid produced low levels of the epoxygenase metabolite 14,15-epoxy-5,8,
11-(Z,ZZ)-eicosatrienoic acid (14,15-EpETrE) as determined by HPLC ana
lysis and gas chromatography mass spectrometry. When authentic 14,15-[
H-3]EpETrE was incubated with these cells in the absence of serum it w
as metabolised initially to the dihydroxy derivative (14,15-dihydroxy-
5,8,11-eicosatrienoic acid, 14,15-DiHETrE) and subsequently to a numbe
r of more polar metabolites as determined by HPLC. Fetal calf serum pr
otected 14,15-EpETrE from metabolism for at least 2 h. A similar patte
rn of metabolism was obtained when 14,15-[H-3]EpETrE was incubated wit
h a human choriocarcinoma cell line (BeWo). Microsomes from this cell
line converted arachidonic acid to a large number of radioactive metab
olites including 14, 15-DiHETrE and 11,12-DiHETrE although there was n
o evidence for the parent epoxides. These results extend earlier findi
ngs that human reproductive tissues produce epoxygenase metabolites, a
nd demonstrate the rapid metabolism of these compounds by intact cells
in the absence of serum.