Tranylcypromine and 15-hydroperoxyarachidonate affect arachidonic acid release in addition to inhibition of prostacyclin synthesis in calf aortic endothelial cells.
In this paper, we examined the effect of two known inhibitors of prostacyclin synthetase, tranylcypromine and 15-hydroperoxyarachidonate, on bradykinin-stimulated prostacyclin synthesis and arachidonic acid release from cellular phospholipids in endothelial cells derived from calf aorta. These two inhibitors inhibit prostacyclin synthesis stimulated by bradykinin, arachidonic acid, and ionophore A23187. However, these two inhibitors also affect the release of arachidonic acid from cells. Using cells prelabeled with [3H]arachidonic acid, we found that bradykinin-stimulated arachidonic acid release is severely inhibited by tranylcypromine (500 microgram/ml) but is stimulated by 15-hydroxyperoxyarachidonate at a concentration as low as 1 microgram/ml. We also found that 15-hydroperoxyarachidonate inhibits not only prostacyclin formation but also prostaglandin formation from the released arachidonic acid. Under the conditions used, these two compounds have no effects on the cell viability as judged by trypan blue exclusion test. We conclude that tranylcypromine and 15-hydroperoxyarachidonate not only inhibit prostacyclin synthesis but also affect other steps in the metabolism of arachidonic acid in whole cells.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D015289:Leukotrienes; D008054:Lipid Peroxides; D010545:Peroxides / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D014191:Tranylcypromine / Q000494:pharmacology*
D001095:Arachidonic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D010545:Peroxides; D011453:Prostaglandins; D000001:Calcimycin; D014191:Tranylcypromine; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D011464:Epoprostenol; D001920:Bradykinin