Influence of nicotine and cotinine on the expression of plasminogen activator activity in bovine aortic endothelial cells.
The effects of nicotine and its major metabolite, cotinine, were evaluated on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in cultured bovine aortic endothelial cells. Both compounds increased PA secretion, determined by 125I fibrin plate assay, in a time- and dose-dependent manner. Maximum effects after 24 hr incubation were observed for nicotine at 10(-8) M and for cotinine at 10(-7) M, which corresponded to about 2.6-fold increases over control for both compounds. The pharmacological PA stimulation required both RNA and protein syntheses, as evidenced by inhibition by actinomycin D and cycloheximide. Both control and treated cells produced multiple forms of PA, as evaluated by SDS-PAGE zymography, and a single form of PAI, as evidenced by reverse fibrin autography. Although activities of all species of PA were enhanced by nicotine and cotinine, these compounds had no significant effects on the release of PAI. These results thus suggest that nicotine and cotinine may have fibrinolytic activity in vivo.
Kuo
B S
BS
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Dryjski
M
M
Bjornsson
T D
TD
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003367:Cotinine / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D011760:Pyrrolidinones / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000378:metabolism
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D011760:Pyrrolidinones; D003561:Cytarabine; D003609:Dactinomycin; D009538:Nicotine; D003513:Cycloheximide; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D003367:Cotinine