Comparison of kidney, lung and liver coumarin 7-hydroxylases in phenobarbital pretreated DBA/2J and C57BL/6J mice

Abstract

In this paper we describe catalytic and immunological properties of coumarin 7-hydroxylase, a cytochrome P-450 dependent enzyme activity, in the liver, kidney and lung of C57BL/67 and DBA/2J mice. Coumarin 7-hydroxylase activity was higher in D2 than in B6 mice in all three organs. For both strains of mice, liver had the highest enzyme activity when expressed per milligram of microsomal protein. However, when expressed per nmole cytochrome P-450 there was no difference in the enzyme activity between the tissues. Inhibition of microsomal coumarin 7-hydroxylase by antibodies previously developed in our laboratory against a cytochrome P-450 fraction from D2 and B6 mouse liver, associated with coumarin 7-hydroxylase, occurred as follows. In D2 mice both antibodies caused approximately 50% inhibition of the enzyme activity of all three organs. In B6 mice, however, the only organ where considerable inhibition took place was the liver, and only when antibody against B6 cytochrome P-450 was used. Ouchterlony immunodiffusion analysis revealed a 100% crossreactivity between the two strains of mice when similar organs were compared. The 100% crossreactivity was also found between the liver and lung in both strains of mice. However, only a 50% crossreactivity was found between kidney and liver or kidney and lung in B6 and between the kidney and lung in D2. The data demonstrate interorgan and interstrain differences in the immunological and catalytical properties of cytochrome(s) P-450 catalysing coumarin 7-hydroxylation.