Effect of various plasminogen activators on prostacyclin synthesis in cultured vascular cells.
In this study, we examined the effects of various plasminogen activators on arachidonic acid release and prostacyclin biosynthesis in cultured rat aortic smooth muscle cells and bovine pulmonary artery endothelial cells. Prostacyclin was the major product formed from arachidonic acid in aortic smooth muscle cells and endothelial cells. When intact cells were incubated with streptokinase, one of the plasminogen activators, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1-5,000 units/ml). Streptokinase also caused a marked release of arachidonic acid. However, when it was incubated with cell-free homogenates and [3H]arachidonic acid, it did not show any effects on prostacyclin biosynthesis. The addition of urokinase and tissue-type plasminogen activator had no effect on prostacyclin biosynthesis. Urokinase stimulated the release of arachidonic acid from cells, but it did not show any effect on prostacyclin release at any concentration of urokinase (1-5,000 units/ml). The release of arachidonic acid and the increased prostacyclin synthesis were not observed when tissue-type plasminogen activator was added. These results indicate that, among various plasminogen activators investigated, only streptokinase causes the release of arachidonic acid and prostacyclin. This could be a beneficial effect in thrombolytic therapy.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002470:Cell Survival; D002474:Cell-Free System; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010960:Plasminogen Activators / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D001616:beta-Galactosidase; D010960:Plasminogen Activators