Cytochrome P-450 and drug metabolism in intestinal villous and crypt cells of rats: effect of dietary iron.

In in tes t ina l mucosa of fed adult rats, cytochrome P-450 content and ac t i v i t y of benzpyrene hydroxyl ase and p-n i t roaniso le O-demethylase are highest in the upper small in test ine and progressively decrease toward the terminal ileum. Among the mucosal cell populations, mature v i l l ous t i p cel ls contain 6 to I0 times more cytochrome P-450 and drug-metabolizing ac t i v i t y per mg microsomal protein than ep i the l ia l crypt ce l ls . On res t r i c t ion of dietary iron intake for 48 hr, cytochrome P-450 content and drug-metabolizing enzyme ac t i v i t y of v i l lous t i p cel ls decrease to 42% and 13% of control values, but are restored within 24 hr by oral iron supplementation. These f indings suggest that intest ina l drug metabolism is local ized pr imar i ly in upper v i l lous cel ls of duodenal mucosa, that cytochrome P-450 is synthesized in maturing ep i the l ia l cel ls as they migrate to the top of the mucosal v i l l u s and that th is process is c r i t i ca l ly dependent on dietary (luminal) i ron.