The regulation of arachidonic acid metabolism in human first trimester trophoblast by cyclic AMP.
Human trophoblast cells are known to release a range of arachidonic acid metabolites into culture medium, including cyclo-oxygenase, lipoxygenase and epoxygenase products. In this study we investigated the effects of dibutyryl cyclic AMP (db cAMP) on arachidonic acid metabolism in human first trimester trophoblast cells, and also determined the distribution of metabolites between intracellular and extracellular compartments. db cAMP increased intracellular levels of radioactivity within 2 min, and extracellular levels of radioactivity were increased after 30 min. These changes were reflected in increased levels of arachidonic acid metabolites in both compartments, indicating that arachidonic acid was metabolised. db cAMP increased intracellular levels of 5,6-epoxyeicosatrienoic acid (5,6-EpETrE) within 2 min of addition to cultured cells. No changes were detected after 5-10 min, but substantial changes were found 30 min after the addition of db cAMP. The dihydroxyeicosatrienoic acid (DiHETrE) breakdown products also increased with similar kinetics. In contrast, levels of 14,15-EpETrE increased after 5-10 min.
Fertility Centre, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. mark.sullivan@ic.ac.uk
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Zosmer
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Sullivan
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014316:Tritium; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D014316:Tritium; D016718:Arachidonic Acid; D003994:Bucladesine; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid