Stimulation of plasmin activity by aspirin.
This study demonstrates an enhancing effect of aspirin on the amidolytic activity of plasmin. The stimulation of plasmin by aspirin was concentration-dependent and was attained at aspirin concentrations above 2 x 10(-4) M. Aspirin produced a small, reproducible and statistically significant stimulation of the chromogenic activity of plasmin upon H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide (S-2251) or pyro-Glu-Gly-Arg-p-nitroanilide (S-2444). Kinetic analysis demonstrated a slight decrease in the affinity of plasmin for substrate S-2251 in the presence of aspirin, reflected by a change of the Km from 3.2 x 10(-4) M to 3.8 x 10(-4) M, and an increase of the Vm. The reciprocal Lineweaver-Burk curve indicated an uncompetitive type of stimulation. The stimulatory effect of aspirin was abolished by the lysine analogue 6-aminohexanoic acid (AHA) but not by the alpha-amino acid glutamic acid. The effect of AHA suggests a specific involvement of lysine binding sites (LBS) on plasmin in the interaction of the enzyme with aspirin. Transient acidification of plasmin abolished its response to aspirin, to AHA and to their combination. The addition of aspirin to diluted human control or pregnancy plasma in vitro stimulated the plasma-mediated cleavage of the chromogenic substrate S-2251. In contrast to its effect on plasmin, aspirin failed to change the activity of tissue-type or urokinase-type plasminogen activators. It is conceivable that in addition to the antithrombotic effect of aspirin ascribed to its interaction with the platelets, aspirin also directly stimulates plasmin activity.
Milwidsky
A
A
Department of Obstetrics, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Finci-Yeheskel
Z
Z
Mayer
M
M
D000595:Amino Acid Sequence; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002863:Chromogenic Compounds; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism
D002863:Chromogenic Compounds; D009842:Oligopeptides; C018788:valyl-leucyl-lysine 4-nitroanilide; C028190:5-oxo-prolyl-glycyl-arginine-4-nitroanilide; D010960:Plasminogen Activators; D005341:Fibrinolysin; D001241:Aspirin