Differences in the response of hepatic and intestinal drug metabolizing enzymes in rats following carbon tetrachloride and/or phenobarbital treatment.

The activities of the microsomal drug metabolizing enzymes in the liver and intestinal mucosa of rats were studied after the intraperitoneal administration of carbon tetrachloride and/or subcutaneous phenobarbital administration. The membrane phospholipid content was decreased after carbon tetrachloride treatment indicating destruction in the membrane structure. Aryl hydrocarbon hydroxylase activity was decreased in the liver and intestinal mucosa after treatment with CCl4 alone and in combination with phenobarbital. The CCl4 treatment increased the intestinal epoxide hydratase activity but decreased the activity in the liver. The hepatic UDPglucuronosyltransferase was slightly induced by phenobarbital and the activity was elevated by the CCl4 treatment. In the intestinal mucosa the enhanced UDPglucuronosyltransferase activity was observed only after phenobarbital pretreatment and the activity was decreased by CCl4. These results support the view that epoxide hydratase and UDPglucuronosyltransferase enzymes occupy different locations in the endosplasmic reticulum of intestinal mucosa than of liver.