Effects of uridine diphosphate glucuronosyltransferase activity on the maximal secretion rate of bilirubin conjugates in the rat

Gastroenterology
W Van Steenbergen, J Fevery

Abstract

It is generally accepted that biliary secretion is rate-limiting for the plasma-to-bile transport of a saturating load of bilirubin. Previous studies from this laboratory have suggested a relationship between the hepatic bilirubin uridine diphosphate glucuronosyltransferase activity and the apparent maximal rate of bilirubin secretion (excretory transport maximum). The present study was undertaken to further investigate this relationship in rats with a wide range of transferase levels and to analyze the effects of transferase activity on the formation of bilirubin monoglucuronides and diglucuronides in vivo and in vitro. Animals with moderately decreased enzyme activity still showed a near-normal excretory transport maximum but decreased fractional amounts of conjugated bilirubins in plasma and liver and a decreased ratio of bilirubins diconjugates to monoconjugates in bile, liver, and plasma. A more pronounced decrease in the level of transferase activity yielded lower excretory transport maximum values as well. Enhanced transferase activities were obtained by pretreatment with a series of enzyme-inducing agents, usually at dosages not influencing bile flow. An enhanced transferase activity produced significant increases in bi...Continue Reading

Citations

Jul 19, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marta Bellodi-PrivatoNicolas Ferry
Apr 25, 2008·Liver International : Official Journal of the International Association for the Study of the Liver·Johan Fevery
Jan 21, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Norikazu MatsunagaIkumi Tamai
Jun 25, 1998·Research in Experimental Medicine. Zeitschrift Für Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie·A WatanabeT Tsuji
Aug 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J González, J Fevery
Mar 1, 1993·JPEN. Journal of Parenteral and Enteral Nutrition·J M CulebrasJ Gonzalez-Gallego
Jun 24, 2003·Biochemical Pharmacology·Viviana A CataniaAldo D Mottino
Sep 6, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tuan Huy NguyenNicolas Ferry
Jul 1, 1991·Journal of Hepatology·M J TuñonJ Gonzalez

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