Inhibition of prostacyclin synthesis in cultured bovine aortic endothelial cells by vitamin K1.
Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet aggregation, is the predominant metabolite of arachidonic acid (AA) in endothelial cells derived from large blood vessels. Vitamin K1 (1-100 microM) inhibited the release of PGI2 and prostaglandin E2 (PGE2) by bovine aortic endothelial cells in culture, as measured by radioimmunoassay of 6-keto-prostaglandin F1 alpha (6-keto-PGE1 alpha) and PGE2. The conversion of exogenous AA to PGI2 was not affected by vitamin K1 as measured by radioimmunoassay and high performance liquid chromatography of radiolabeled AA metabolites. Similarly, vitamin K1 did not affect the conversion of prostaglandin H2 (PGH2) by in vitro enzyme systems. However, vitamin K1 inhibited the calcium ionophore A23187-induced release of [3H]AA from membrane phospholipids of bovine aortic endothelial cells. Inhibition of [3H]AA release from other cells of vascular origin was also observed after exposure to vitamin K1, but this effect was not observed in cells of non-vascular origin, including platelets. Therefore, vitamin K1 modulates the release of AA in vascular cells and thus inhibits the capacity of blood vessels to synthesize PGI2.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D015232:Dinoprostone; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019746:Intramolecular Oxidoreductases; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis; D011863:Radioimmunoassay; D010837:Vitamin K 1 / Q000494:pharmacology*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D016718:Arachidonic Acid; D000001:Calcimycin; D010837:Vitamin K 1; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D010740:Phospholipases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D015232:Dinoprostone