Inhibitory effect of aprotinin and gabexate mesilate on human plasma kallikrein.
Prekallikrein (PK) in human plasma was activated with kaolin in the presence of protease inhibitors aprotinin (Trasylol) and gabexate mesilate to investigate a difference in the inhibitory activity of plasma kallikrein (K) between these inhibitors. Benzoyl-prolyl-phenylalanyl arginine-p-nitroanilide (PPAN) cleavage of purified plasma K was markedly inhibited by aprotinin and gabexate mesilate, and acetyl-glycyl-l-lysine methyl ester hydrolysis of purified PK activator was slightly inhibited. PPAN cleavage of plasma K-alpha2 macroglobulin complex was hardly inhibited by aprotinin while PPAN cleavage of the complex was markedly inhibited by gabexate mesilate. The inhibitory activity of gabexate mesilate towards plasma K completely disappeared after 10 min incubation with plasma at 37 degrees C and also in 30 min on the experiment in which the time course of kaolin-induced PK activation was observed at 10 degrees C. On the other hand, the inhibitory activity of aprotinin towards plasma K never changed after 10 min incubation with plasma at 37 degrees C or 30 min incubation with plasma at 10 degrees C. From the results it is concluded that a predominant effect of aprotinin in human plasma is due to its stability in contrast to instability of gabexate mesilate.
D000328:Adult; D007611:Aprotinin / Q000494:pharmacology*; D005174:Factor XII / Q000378:metabolism; D015956:Factor XIIa; D016670:Gabexate; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D013997:Time Factors
D006146:Guanidines; D010446:Peptide Fragments; D016670:Gabexate; D005174:Factor XII; D007611:Aprotinin; D007610:Kallikreins; D015956:Factor XIIa