Biliary excretion of a stretched bilirubin in UGT1A1-deficient (Gunn) and Mrp2-deficient (TR-) rats.
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.
McDonagh
A F
AF
GI Unit and Liver Center, Univeristy of California, San Francisco 94143-0538, USA. tonymcd@itsa.ucsf.edu
Lightner
D A
DA
Nogales
D F
DF
Norona
W S
WS
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D001663:Bilirubin / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D014453:Glucuronosyltransferase / Q000235:genetics / Q000502:physiology*; D008968:Molecular Conformation; D051381:Rats; D011911:Rats, Gunn; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D000099148:UGT1A1 Enzyme
D018528:ATP-Binding Cassette Transporters; D001663:Bilirubin; D002352:Carrier Proteins; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C423013:Abcc2 protein, rat; C499946:Ugt1a1 protein, rat