Effects of bilirubin on glucuronidation of p-nitrophenol and morphine.
Addition of bilirubin in vitro to hepatic microsomes or 9,333 g supernatant activated UDP glucuronyltransferase activity (UDPGT) for p-nitrophenol of livers from Sprague-Dawley rats, Wistar rats, icteric Gunn rats and nonicteric Gunn rats. However, injection of bilirubin at subtoxic doses using a variety of regimens failed to produce detectable activation of UDPGT in intact or bile duct-ligated rats. Pretreatment with intraperitoneal injections of bilirubin increased the rate of morphine glucuronide excretion in both Sprague-Dawley and icteric Gunn rats. Sulfadimethoxine did not affect morphin e excretion in Gunn rats. The data suggest that activation of UDPGT is of little, if any, significance in hyperbilirubinemia although the basis for increased excretion of morphine following bilirubin pretreatment has not been established.
D000818:Animals; D001652:Bile Ducts; D001663:Bilirubin / Q000378:metabolism / Q000494:pharmacology*; D005965:Glucuronates / Q000096:biosynthesis; D014453:Glucuronosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007565:Jaundice / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009020:Morphine / Q000378:metabolism*; D009596:Nitrophenols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013412:Sulfadimethoxine / Q000494:pharmacology; D013997:Time Factors
D005965:Glucuronates; D009596:Nitrophenols; D013412:Sulfadimethoxine; D009020:Morphine; D014453:Glucuronosyltransferase; D001663:Bilirubin