title: Cytochrome P450 metabolites of arachidonic acid in human placenta.
abstract: Little is known about the epoxygenase pathway of the arachidonic acid cascade in uterine tissues. In this paper, we describe the formation of epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in human term placenta after uncomplicated pregnancies. Metabolism of [3H]-arachidonic acid was analyzed in short term tissue cultures of placenta by reverse phase HPLC. Major metabolites coeluted with authentic EETs and DHETs. The formation of EETs was inhibited by carbon monoxide. In non-radioactive incubations with biopsies from seven different placentas, sufficient material for GC/MS analysis was obtained. The combined media were purified by solid phase extraction and reverse phase HPLC. The fraction coeluting with DHETs was derivatized with pentafluorobenzylbromide (PFB) and bis-(trimethylsilyl)-trifluoroacetylacetamide (BSTFA) and analyzed by GC/NICI/MS/MS. 11, 12-DHET and 14, 15-DHET were identified by their mass spectra displaying specific fragments at m/z 149 and m/z 189, respectively. Our results suggest that the epoxygenase pathway is active in human term placenta.
authors.affiliation: Department of Obstetrics & Gynecology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: W R
authors.initials: WR
authors.lastname: Schaefer
authors.forename: K
authors.initials: K
authors.lastname: Werner
authors.forename: H
authors.initials: H
authors.lastname: Schweer
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: E
authors.initials: E
authors.lastname: Arbogast
authors.forename: H P
authors.initials: HP
authors.lastname: Zahradnik
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D010105:Oxygenases / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D014316:Tritium
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D014316:Tritium; D016718:Arachidonic Acid; D000001:Calcimycin; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid