Eicosapentaenoic acid: its effects on arachidonic acid metabolism by cells in culture.

Some eukaryotic cells in culture synthesize a variety of lipoxygenase and/or cyclooxygenase products when stimulated by appropriate agonists. Under normal nutritional conditions, these products are derived from the polyunsaturated fatty acid (PUFA) 5,8,11,14-eicosatetraenoic acid (ETA), arachidonic acid, which before metabolism must be liberated from cellular lipids by deesterification. If the cellular lipids are preloaded with 5,8,11,14,17-eicosapentaenoic acid (EPA) and cells are then stimulated to metabolize the PUFAs, levels of cyclooxygenase and lipoxygenase products synthesized are altered. Cyclooxygenase products decrease, while lipoxygenase products are not significantly affected and may even increase. The decrease in the production of cyclooxygenase products results from reduced utilization of the substrate (ETA). Decreased prostaglandin production by rat basophil leukemia-1 cells preloaded with EPA and radiolabeled with [3H]ETA and [14C]EPA can also be demonstrated by high-performance liquid chromatographic analyses of [3H]- and [14C] radiolabeled metabolites in culture fluids of cells stimulated to metabolize PUFA by the Ca2+ ionophore A23187.