Dihomo-δ-linolenic acid increases the metabolism of eicosapentaenoic acid in perfused vascular tissue

Abstract

The isolated rabbit ear was perfused with 14C-arachidonic acid (AA), with 14C-eicosapentaenoic acid (EPA) or with 14C-dihomo-δ-linolenic acid (DGLA). After incorporation of 14C-AA, the ionophore A 23187 (10 μg) stimulated the release of products comigrating with authentic PGI 2 (measured as 6-keto-PGF 1α), PGF 1α and PGE 2 on the thin layer chromatography plate. After inc orporation of 14C-EPA, A 23187 did not release any trienoic 14C-PGs. After incorporation of 14C-DGLA, A 23187 stimulated the release of labeled products comigrating with 6-keto-PGF 1α (but not PGF 1α), PGE 1 and PGD 1. Infusion of unlabeled AA (1 and 10 μg/ml) did not influence the metabolism of 14C-EPA or 14C-DGLA. Infusion of unlabeled DGLA (10 μug/ml) strongly stimulated the release of trienoic 14C-PGs but did not significantly increase the release of bisenoic 14C-PGs. Neither DGLA nor AA influenced the release of any other labeled incorporated PG precursor, indicating that a phospholipase A 2 was not affected. The results show that DGLA is able to stimulate the metabolism of incorporated 14C-EPA resulting in an increased release of antiaggregatory trienoic PGs. The mechanism of this effect is unclear but it may be mediated via the formation of a hydroperoxide derivative of DGLA. Thus, an increased generation of antithrombotic trienoic PGs may be expected under special conditions, possibly also in vivo , depending on the supply of unsaturated fatty acids or the level of various hydroperoxide derivatives.