フィブリノーゲン‐トロンビン系におけるヘパリンおよびヘパリノイドの効果

Abstract

Inhibition constants of heparin and heparinoids, which formed soluble complexes with fibrinogen, for the fibrinogen and thrombin system were determined by the turbidimetrical method, derived from a kinetic study on the initial stage of the fibrinogen-fibrin conversion. A commercial heparin (molecular weight, 9, 000; 152units/mg) and dextran sulfate (DSC), low molecular weight dextran sulfate (DSA), carboxy methyl cellulose (CMC), chondroitin sulfate (CHS), and sulfated methyl cellulose (SMC) were investigated. Among heparinoids, DSC inhibited more effectively the reaction of fibrinogen and thrombin than heparin. At high concentrations (>0.08mg/ml), heparin and heparinoids acted as noncompetitive inhibitors, and inhibition constants for those substances were smaller in the following order of DSV<heparin<DSA<CMC<CHS<SMC.The apparent inhibition of heparin and DSC for the reaction of fibrinogen and thrombin increased with decreasing concentrations. At low concentrations (<10-4mg/ml), both heparin and DSC acted as hyperbolic competitive inhibitors of thrombin. The inhibition constant of heparin was 1.07×10-8M, which agrees with values estimated from a thrombin and synthetic substrate system. The scarce inhibition effect of DSC in the presence of antithrombin III for the fibrinogen-thrombin system suggests that DSC can not induce the conformational change of antithrombin III, different from heparin.