title: Influence of plasma proteinase inhibitors and aprotinin on trypsin-induced bradykinin release in vitro in man.
abstract: The consumption of kininogen (measured as kinin-releasable material) was studied in an experimental model in vitro. Analyses were made following the addition of increasing amounts of human cationic trypsin to human serum and plasma. The consumption of kininogen was correlated with the degree of saturation of the plasma proteinase inhibitors alpha 2-macroglobulin (alpha 2-M) and alpha 1-proteinase inhibitor (alpha 1-PI) with trypsin in the presence and absence of aprotinin (Trasylol). The level of kininogen fell dramatically when alpha 2-M was saturated to 70% in spite of 90% free alpha 1-PI. Trypsin-alpha 2-M complexes had no effect on kininogen levels. 60 mumol/l of aprotinin, i.e. approximately 3 X 10(6) KIU/l, blocked only 60% of the trypsin-induced kininogen consumption in serum, while 15 mumol/l of aprotinin blocked 100% of this consumption in plasma. With increasing concentration of aprotinin in serum, a decreasing consumption of alpha 2-M and especially of alpha 1-PI was observed on the addition of trypsin. The high aprotinin concentration needed to block trypsin-induced kininogen cleavage in human serum or plasma may explain the poor clinical effect of aprotinin to date in human acute pancreatitis.
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood* / Q000502:physiology; D011817:Rabbits; D014357:Trypsin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D007704:Kininogens; D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; D007611:Aprotinin; D014357:Trypsin; D001920:Bradykinin