Inhibition of rat hepatocyte organic anion transport by bile acids

K. Ishii, A. W. Wolkoff

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Hepatocytes extract, metabolize, and excrete various bile acids and non- bile acid organic anions. The transporters for these two classes of compounds are unrelated, although the bromosulfophthalein (BSP)/bilirubin transporter can mediate Na+-independent transport of several bile acids. This may explain previous observations of inhibition of organic anion uptake by bile acids. It has been suggested that ursodeoxycholic acid (UDCA), which has been used to treat various hepatobiliary disorders, may not have this inhibitory effect. This possibility has now been studied. The influence of acute and chronic (overnight) exposure to UDCA and other bile acids on extraction of BSP from albumin by cultured rat hepatocytes has been examined. Two hepatocyte uptake systems have been identified, one of high affinity and low capacity and one of lower affinity and high capacity. The present study indicates that bile acids inhibit the high-affinity system but have little effect on the low-affinity system. These data suggest that extraction of organic anions from the circulation is modulated by bile acids. In states of cholestasis, where serum bile acid levels are abnormally high, organic anion uptake may be reduced as a consequence. This may serve to limit entry into the cell of potentially toxic compounds, such as bilirubin, for which detoxification and excretory mechanisms are compromised.

Original languageEnglish (US)
Pages (from-to)G458-G464
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume267
Issue number3 30-3
DOIs
StatePublished - 1994

Keywords

  • albumin
  • bilirubin
  • bromosulfophthalein
  • ursodeoxycholic acid

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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