Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of vasoactive agents on plasminogen activator (PA) release was studied in isolated perfused pig ears. In the perfusion with atropine (3 microM)-containing Tyrode's solution, the enhancement of PA release caused by acetylcholine (1.0 micrograms) was completely inhibited; however, increases caused by other potentiators, namely, bradykinin (1.0 micrograms), histamine (1.0 micrograms), dilazep (30 micrograms), and thrombin (6 U) were not affected. In the case of mepyramine (10 microM), the increase of PA release caused by histamine (1.0 micrograms) was completely inhibited; and that caused by dilazep (30 micrograms) was partially inhibited, however, increases caused by acetylcholine, bradykinin, and thrombin were not influenced. Papaverine (30 microM) which could completely abolish the hypertensive effect of norepinephrine (1.0 micrograms) exerted a partial inhibition of the enhancement of PA release caused by dilazep; however, it did not affect those caused by other agents. Quinacrine (50 microM) and indomethacin (100 microM) did not have any effects on the enhancements of PA release caused by the five potentiators.
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PMID:A possible mechanism of vasoactive agents on plasminogen activator release in isolated perfused pig ears. 668 79

Urokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle - not the catalytic - domain of uPA. We used an in-vivo uPA overexpression model to test the hypothesis that uPA-induced vasoconstriction is a reversible vasomotor process that can be prevented - and uPA fibrinolytic activity preserved - by: 1) removing the growth factor and kringle domains; or 2) anchoring uPA to the endothelial surface. To test this hypothesis we constructed adenoviral vectors that express: wild-type rabbit uPA (AduPA); a uPA mutant lacking the NH(2)-terminal growth-factor and kringle domains (AduPAdel); a mutant lacking catalytic activity (AduPAS-->A), and a cell-surface anchored mutant (AdTMuPA). uPA mutants were expressed and characterised in vitro and in carotid arteries in vivo. uPAS-->A had no plasminogen activator activity. Activity was similar for uPA and uPAdel, whereas AdTMuPA had only cell-associated activity. AduPAS-->A arteries were not constricted. AduPA, AduPAdel, and AdTM-uPA arteries were constricted (approximately 30% smaller lumens; p< or =0.008 vs. AdNull arteries). Papaverine reversed constriction of AduPA arteries. uPA-mediated arterial constriction is a vasomotor process that is mediated by uPA catalytic activity, not by the NH(2)-terminal domains. Anchoring uPA to the endothelial surface does not prevent vasoconstriction. uPA catalytic activity, generated by artery wall cells, may contribute to lumen loss in human arteries. Elimination of uPA vasoconstrictor activity requires concomitant loss of fibrinolytic activity.
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PMID:Constriction of carotid arteries by urokinase-type plasminogen activator requires catalytic activity and is independent of NH(2)-terminal domains. 1988 38