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Hepatic disposition and biliary excretion of bilirubin and bilirubin glucuronides in intact rats. Differential processing of pigments derived from intra- and extrahepatic sources

Academic Article
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Overview

authors

  • Crawford, J. M.
  • Ransil, B. J.
  • Potter, Clinton
  • Westmoreland, S. V.
  • Gollan, J. L.

publication date

  • April 1987

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Mechanisms for transport of bilirubin and its conjugates in hepatocytes have not been defined. We investigated the hepatic processing of bilirubin glucuronides and their precursors, and characterized the disposition of bile pigments arising from intraversus extrahepatic sources. Tracer doses of purified radiolabeled biliverdin, bilirubin, bilirubin monoglucuronide (BMG) or diglucuronide (BDG) were administered intravenously to intact normal or jaundiced homozygous Gunn rats. Rapid sequential analysis of radiolabeled BMG and BDG in bile revealed comparable excretion patterns following biliverdin and bilirubin injection, with BDG as the major pigment. Biliary excretion of radiolabeled conjugates from injected BMG was more rapid, with BMG predominating. Excretion of injected BDG in normal rats and BMG or BDG in Gunn rats was virtually identical to that of unaltered BMG in normal rats. Model independent analysis by deconvolution provided objective comparison of the disposition of radiolabeled pigments from the different sources. These findings indicate that bilirubin glucuronides formed in the liver from endogenous (hepatic) and exogenous (extrahepatic) sources of bilirubin follow a similar excretory pathway. BMG formed endogenously is converted preferentially to BDG, whereas circulating BMG is excreted predominantly unchanged. Exogenous conjugated bilirubins are excreted more rapidly than those generated intrahepatically, by a transcellular pathway that is largely independent of the conjugation system.

subject areas

  • Animals
  • Bile
  • Bile Pigments
  • Bilirubin
  • Liver
  • Rats
  • Rats, Gunn
  • Rats, Inbred Strains
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Identity

PubMed Central ID

  • PMC424303

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci112934

PubMed ID

  • 3558820
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Additional Document Info

start page

  • 1172

end page

  • 1180

volume

  • 79

issue

  • 4

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