Urokinase activity was assayed by a two-stage globinolytic method and by a direct
chromogenic assay. With both methods, the enzyme activity was found to be inhibited
by penicillins. The inhibition by penicillin G, carbenicillin, cloxacillin and penicilloic
acid was dose-dependent. The Kj of penicillin G and urokinase with the S-2444 as substrate
is 4 mM. This compound exhibited a competitive pattern of inhibition. Ampicillin and
6-amino penicillanic acid failed to inhibit urokinase. These results imply that hydrophobic
side chains of penicillins interact with the active site of urokinase. The present
observation could be relevant in clinical situation in which high doses of beta-lactam
antibiotics could modulate the endogenous fibrinolytic activity of circulating urokinase.
Keywords
Urokinase - Penicillins - β-lactam antibiotics