FIGURE 10.
Inhibition by warfarin of VKOR activity in testis of OFA Sprague-Dawley rats. VKOR activity versus vit K1>O (from 0 to 200 μm) was determined in the presence of four different concentrations of warfarin incubated with rat liver microsomes. Each data point represents the mean ± S.D. (error bars) of two determinations. A, the experimental results were fitted by nonlinear regression using the noncompetitive inhibition model, and the Km and Ki parameters were determined for recombinant rat VKORC1 (i.e. 19.6 and 0.6 μm). B, the experimental results were fitted by nonlinear regression using the noncompetitive inhibition model, and the Km and Ki parameters were determined for recombinant rat VKORC1L1 (i.e. 35 and 33 μm). C, the experimental results were fitted considering a mixed expression of VKORC1 and VKORC1L1 in testis by nonlinear regression using the noncompetitive inhibition model, the catalytic parameters of recombinant rVKORC1 and rVKORC1L1. The best fit was obtained in testis for a ratio of 45% of the VKOR activity supported by VKORC1 and 55% supported by VKORC1L1.