Docosapentaenoic acid (22:5,n-3): metabolism and effect on prostacyclin production in endothelial cells.
Eicosapentaenoic acid (EPA, 20:5,n-3) and docosahexaenoic acid (DHA, 22:6, n-3), the two main fatty acids of fish oil, have been shown to inhibit prostacyclin production and to be actively interconverted, leading to the accumulation of docosapentaenoic acid (DPA, 22:5,n-3) in endothelial cell phospholipids. We have investigated the effect of supplementing endothelial cells with DPA on their capacity to produce prostacyclin. We found that endothelial cells incubated for 22 h with 25 microM DPA bound to albumin (fatty acid/albumin ratio of 1.3) produced two-fold less prostacyclin compared to control cells when stimulated with endogenous arachidonic acid-mobilizing agents such as bradykinin and calcium ionophore A23187. Since the formation of prostacyclin from 0.1-15 microM exogenous arachidonic acid was also reduced, it is suggested that prostacyclin inhibition observed in DPA-treated cells might not proceed from a reduction of arachidonic acid availability only. Such an inhibition was already observed after 1 h incubation of the cells with DPA, and with 2-20 times lower DPA concentrations. The inhibition might depend on EPA which was formed by retroconversion of DPA.
Bénistant
C
C
Université de Montpellier I, Faculté de Pharmacie, Montpellier, France.
Achard
F
F
Ben Slama
S
S
Lagarde
M
M
D000818:Animals; D001011:Aorta / Q000166:cytology; D016718:Arachidonic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D000001:Calcimycin; D011464:Epoprostenol; C026219:docosapentaenoic acid; D001920:Bradykinin