The major plasma kallikrein inhibitor of guinea pig plasma

Abstract

A plasma kallikrein inhibitor in guinea pig plasma (KIP) was purified to homogeneity. KIP is a single chain protein and the apparent molecular weight is estimated to be 59000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In amino acid composition, KIP is similar to human and mouse α1-proteinase inhibitors and mouse contrapsin. KIP forms an equimolar complex with plasma kallikrein in a dose- and time-dependent fashion. The association rate constants for the inhibition of guinea pig plasma kallikrein by KIP, α2 CI-inactivator and antithrombin III were 2.5 ± 0.3 · 104, 2.4 ± 0.4 · 104, 6.6 ± 0.5 · 104 and 9.1 ± 0.6 · 102, respectively. Comparison of the association rate constants and the normal plasma concentrations of the four inhibitors demonstrates that KIP is ten-times as effective as α2-MG and other two inhibitors are marginally effective in the inhibition of kallikrein. KIP inhibits trypsin and elastase rapidly, and thrombin and plasmin slowly, but is inactive for chymotrypsin and gland kallikrein. These results suggest that KIP is the major kallikrein inhibitor is guinea pig plasma and the proteinase inhibitory spectrum is unique to KIP in spite of the molecular similarity to α1-proteinase inhibitor.