Biliary excretion of a stretched bilirubin in UGT1A1-deficient (Gunn) and Mrp2-deficient (TR-) rats

FEBS Lett. 2001 Oct 12;506(3):211-5. doi: 10.1016/s0014-5793(01)02916-7.

Abstract

The metabolism and biliary excretion of a stretched bilirubin analog with a p-xylyl group replacing the central CH2 hinge were investigated in normal rats, Gunn rats deficient in bilirubin conjugation, and TR- rats deficient in bilirubin glucuronide hepatobiliary transport. Unlike bilirubin, the analog was excreted rapidly in bile unchanged in all three rat strains after intravenous administration. In TR- rats biliary excretion of the analog was diminished, but still substantial, demonstrating that the ATP-binding cassette transporter Mrp2 is not required for its hepatic efflux. These effects are attributable to differences in the preferred conformations of bilirubin and the analog.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Animals
  • Biliary Tract / metabolism*
  • Bilirubin / chemistry
  • Bilirubin / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Chromatography, High Pressure Liquid
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / physiology*
  • Molecular Conformation
  • Rats
  • Rats, Gunn
  • Rats, Sprague-Dawley
  • Species Specificity

Substances

  • ATP-Binding Cassette Transporters
  • Abcc2 protein, rat
  • Carrier Proteins
  • Ugt1a1 protein, rat
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin