Interaction of SK-human plasmin, SK-dog plasmin complexes with alpha 2-antiplasmin and alpha 2-macroglobulin.
In patients treated with streptokinase there is a rapid and significant decrease in the level of fibrinogen in the circulation. In dogs given streptokinase there is no such change in circulating fibrinogen. To find an explanation for this species difference in response to streptokinase, the inhibition of SK-human plasmin and SK-dog plasmin by soybean trypsin inhibitor, alpha 2-antiplasmin and alpha2-macroglobulin were compared in this study. Soybean trypsin inhibitor completely blocked the hydrolysis of S-2251 substrate (D-val-L-leu-lys-p-nitroanilide) by SK-dog plasmin and had no effect on SK-human plasmin. Alpha 2-Antiplasmin, the physiologically important regulator of fibrinolysis, inhibited S-2251 hydrolysis by SK-dog plasmin but not the activity of SK-human plasmin. alpha 2-Macroglobulin showed 100% inhibition of proteolytic activity and 50% inhibition of S-2251 activity of SK-dog plasmin, and had no effect on SK-human plasmin. Studies with fresh human and dog plasma also showed that the SK-dog plasmin is rapidly inactivated by the alpha 2-antiplasmin present in the plasma. The inactivation of SK-dog plasmin and not SK-human plasmin by plasma inhibitors explains the differences in the response of dog and humans to the administration of streptokinase.
Reddy
K N
KN
Cercek
B
B
Lew
A S
AS
Ganz
W
W
D000818:Animals; D004285:Dogs; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D009842:Oligopeptides / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D013045:Species Specificity; D013300:Streptokinase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D009842:Oligopeptides; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; C018788:valyl-leucyl-lysine 4-nitroanilide; D010958:Plasminogen; D013300:Streptokinase; D005341:Fibrinolysin