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

FEBS Letters

McDonagh, Antony F.²  Lightner, David A.¹  Nogales, Daniel F.¹  Norona, Wilma S.² 

[1] Department of Chemistry, University of Nevada, Reno, NV 89557-0020, USA;G.I. Unit and Liver Center, S-357, Box 0538, University of California, San Francisco, CA 94143-0538, USA

关键词: Bilirubin;    Glucuronide;    UGT1A1;    Multidrug resistance-associated protein 2;    Gunn rat;    TR− rat;    HPLC;    high performance liquid chromatography;    MRP;    multidrug resistance-associated protein;    UGT;    uridinediphosphoglucuronosyl transferase;   

DOI  :  10.1016/S0014-5793(01)02916-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown