Hepatic morphine and estrone glucuronyltransferase activity and morphine biliary excretion in the isolated perfused rat liver. Effect of pregnancy and estradiol-17 beta treatment.

Hepatic microsomal estrone and morphine glucuronyltransferase activity and the biliary excretion of morphine in the isolated perfused liver were examined in nonpregnant, pregnant (19-21 days of gestation), and estradiol-17 beta-treated (E2; 1.0 mg/kg/day sc for 14 days) rats. Pregnancy decreased estrone and morphine glucuronyltransferase activity 20%, whereas E2 treatment increased activity 50%. Treatment of nonpregnant and pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (3 micrograms/kg po) increased estrone glucuronyltransferase activity 1.3- and 2.8-fold respectively, but such treatment had no effect in E2-treated rats. In the isolated perfused liver, E2 treatment, but not pregnancy, decreased the biliary excretion of morphine 3-glucuronide. Bile flow (microliter/min/g of liver) was slightly decreased by pregnancy but not by E2 treatment. Maximal bile/perfusate concentration ratios of morphine glucuronide were 175, 325, and 90 in livers from nonpregnant, pregnant, and E2-treated rats, respectively.