Effects of sulfonylureas on the synthesis and secretion of plasminogen activator from bovine aortic endothelial cells.
The effects of sulfonylureas on the production of plasminogen activator (PA) and antiactivator (PAI) were investigated using bovine aortic endothelial cells. All compounds studied stimulated PA release (1.3- to 5.2-fold), with glipizide being the most potent, followed by tolazamide, chlorpropamide, and tolbutamide, in that order, while glyburide was the least effective. Both tissue-type and urokinase-type PA production was enhanced. Studies using metabolic inhibitors indicated that both RNA and protein syntheses are required for the sulfonylurea-mediated stimulation of PA release. In addition to continuous release of the two PAs, there was also a continuous release of a single PAI, which did not show an increase after the sulfonylureas. These results suggest that, in addition to their beneficial effects in the treatment of diabetes mellitus, some sulfonylurea compounds may also have significant thrombolytic effects. These results also suggest that pharmacological enhancement of PA production by vascular endothelial cells may be a promising antithrombotic mechanism.
D000818:Animals; D001011:Aorta; D001345:Autoradiography; D002417:Cattle; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology*; D007700:Kinetics; D008970:Molecular Weight; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D015849:Plasminogen Inactivators; D011233:Precipitin Tests; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D015849:Plasminogen Inactivators; D013453:Sulfonylurea Compounds; D003609:Dactinomycin; D003513:Cycloheximide; D010960:Plasminogen Activators