Effects of penicillins and 6-aminohexanoic acid on the kinetics of human plasmin.
Human plasmin activity is inhibited by various penicillins in a dose-dependent manner. Ampicillin and cloxacillin produce a 50% inhibition of the globinolytic activity of plasmin at 4.5 and 5.3 mM respectively. A lower inhibitory capacity is displayed by carbenicillin. Assay of plasmin by its amidolytic activity on D-valyl-L-leucyl-L-lysine p-nitroanilide dihydrochloride showed that ampicillin at a concentration producing half-maximal inhibition converted the hyperbolic activity-substrate concentration curve into a sigmoidal curve. A similar conversion occurred in the presence of ampicillin when plasmin was assayed with an alternative chromogenic substrate, L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride 6-Aminohexanoic acid at 7.5 microM abolished the inhibition of plasmin induced by ampicillin. The present observations suggest that ampicillin interacts with plasmin at a regulatory site different from the active site of the enzyme. The effect of 6-aminohexanoic acid indicates that the lysine-binding site may be part of a regulatory site. It is possible that modulation of plasmin activity by ligands plays a role in the control of fibrinolysis.
Higazi
A A
AA
Department of Clinical Biochemistry, Hadassah-Hebrew University Medical School, Mount Scopus Hospital, Jerusalem, Israel.
Mayer
M
M
D000614:Aminocaproates / Q000494:pharmacology*; D015119:Aminocaproic Acid / Q000494:pharmacology*; D000667:Ampicillin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010406:Penicillins / Q000494:pharmacology*
D000614:Aminocaproates; D010406:Penicillins; D000667:Ampicillin; D005341:Fibrinolysin; D015119:Aminocaproic Acid