title: Inhibitory effect of aprotinin and gabexate mesilate on human plasma kallikrein.
abstract: 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.
mesh_terms: 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
chemical_list: D006146:Guanidines; D010446:Peptide Fragments; D016670:Gabexate; D005174:Factor XII; D007611:Aprotinin; D007610:Kallikreins; D015956:Factor XIIa