Inhibition by n-3 fatty acids of arachidonic acid metabolism in a primary culture of astroglial cells.

Docosahexaenoic acid (22:6 n-3) was present in low concentrations in a primary culture of rat brain astroglial cells, when compared to brain cortex. We have thus supplemented these cells with this fatty acid and investigated the effects of its incorporation in cell phospholipids on the conversion of arachidonic acid, 20:4 n-6, through the cyclo and lipoxygenase pathways, after cell stimulation. Docosahexaenoic acid-enriched cells produced less thromboxane B2 and 6-keto-Prostaglandin F1 alpha and markedly less 12-hydroxyeicosatetraenoic acid than unsupplemented cells, after stimulation with the Ca(2+)-ionophore A23187. The production of 15-hydroxyeicosatetraenoic acid from arachidonic acid was slightly increased in docosahexaenoic acid-supplemented cells. We have also supplemented these cells with eicosapentaenoic acid (20:5 n-3) and, in addition to accumulation of this fatty acid in cell phospholipids, we found elevation of 22:5 n-3 and some increment of 22:6, confirming that glial cells are able to convert eicosapentaenoic acid to the long chain, more unsaturated derivatives. In conclusion, n-3 fatty acids, when supplemented to glial cells, appear to modulate the arachidonic acid cascade and to be converted through the elongation and desaturation pathways.