Serum-dependent induction of plasminogen activator in human fibroblasts by catecholamines and comparison with the effects of prostaglandin E1.
Human foreskin fibroblasts produce the protease plasminogen activator, as shown by the ability of cell extracts to lyse 125I-labelled fibrin in the presence of plasminogen. Cellular plasminogen activator was stimulated up to 3-fold by 0.01-10 microM epinephrine, norepinephrine, or isoproterenol. Increases in plasminogen activator were slow in onset (24 h) and long-lived (greater than 48 h), and were abolished by 10 micrograms/ml of cycloheximide or 1 microgram/ml of actinomycin D, suggesting de novo synthesis of the protease. Stimulation of plasminogen activator by catecholamines was inhibited by 10 microM propranolol but not by 10 microM phentolamine, suggesting the involvement of beta-adrenergic receptors. Catecholamines stimulated plasminogen activator only in the presence of fetal bovine serum; under serum-free conditions they were inhibitory. Serum did not appear to alter the uptake and metabolism of epinephrine during incubation with fibroblasts. The ability of fetal bovine serum to support the induction of plasminogen activator by either 1 microM epinephrine or 3 microM prostaglandin E1 was maintained following dialysis but lost on heating (70 degrees C, 10 min) or acidification (pH 2.5). Human and calf sera supported the stimulatory effects of prostaglandin E1 but not of epinephrine. These results indicate that serum may influence the synthesis of plasminogen activator in cultured cells by modifying their response to vasoactive hormones.
D000527:Alprostadil; D002478:Cells, Cultured; D003470:Culture Media; D004837:Epinephrine / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010960:Plasminogen Activators / Q000096:biosynthesis*; D011433:Propranolol / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D003470:Culture Media; D011458:Prostaglandins E; D011433:Propranolol; D010960:Plasminogen Activators; D000527:Alprostadil; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine