PGI3 production from eicosapentaenoic acid in 3T3 fibroblast cells and cultured bovine pulmonary artery endothelial cells.
Production of PGI3 from eicosapentaenoic acid (EPA) in 3T3 fibroblast cells and in cultured bovine pulmonary artery endothelial cells (CPAE) which had an ability to produce PGI2 from arachidonic acid (AA), was investigated by bioassay, gas chromatography-mass spectrometry (GC-MS) and thin layer chromatography (TLC). Inhibition of platelet aggregation was observed in the supernatant obtained from a culture medium of 3T3 fibroblast cells after incubation with EPA. This active substance in the supernatant could be identified as PGI3, since the inhibitory effect of the supernatant was blocked by tranylcypromine, a potent inhibitor of prostacyclin synthetase. The inhibitory effect on platelet aggregation by the supernatant from culture medium with EPA was low compared with that with AA. More delta 17-6-keto PGF1 alpha from EPA was produced than 6-keto PGF1 alpha from AA at the same concentration of substrates, when the formation of prostacyclins from EPA and AA was measured as their stable metabolites, delta 17-6-keto PGF1 alpha and 6-keto PGF1 alpha by GC-MS respectively. It is suggested that the anti-aggregatory ability of PGI3 is lower than that of PGI2. On the contrary, the amount of PGI3 produced from EPA was significantly less than that of PGI2 produced from AA in CPAE. The production of 6-keto PGF1 alpha from exogenous AA was decreased by increasing the ratio of EPA to AA in the culture medium and the production of delta 17-6-keto PGF1 alpha from EPA also decreased by an addition of AA to the culture medium. This result suggests that AA and EPA compete each other at the site of action of cyclooxygenase.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000031:analogs & derivatives; D005347:Fibroblasts / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; C034240:prostaglandin I3; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol