Effect of thrombin on plasminogen activator release from isolated perfused dog leg

Abstract

Inducement of secondary fibrinolysis can be explained most simply by assuming that a substance newly formed in the process of blood coagulation acts on the endothelial cells and releases plasminogen activator (P. A. ) into the circulatory blood. In the present study, it was found that thrombin caused release of P.A. from isolated dog leg perfused with physiological solution. Following administration of purified thrombin to the isolated perfused dog leg, P.A. was released within 10 sec and reached its peak activity at 15∼30 sec. A dose response in P.A. activity released to thrombin was also detected to some extent (1 unit/ml∼50 units/ml). These results suggest that thrombin mediates secondary fibrinolysis. The effects on P.A. release of DFP-treated thrombin and TLCK-treated thrombin, which are inactive in fibrinogen-fibrin conversion, were examined. These chemically modified forms of thrombin did not release P.A. Furthermore, examination of the effects of acetylated thrombin revealed that it also did not cause P.A. release. These results indicate that P.A. is released from the vascular wall by thrombin so long as the latter maintains an intact active center of proteolysis.