Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1

Gastroenterology. 1999 Oct;117(4):770-5. doi: 10.1016/s0016-5085(99)70333-1.


Background & aims: Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of human LST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis.

Methods: A rat liver cDNA library was screened with human LST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses.

Results: rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with human LST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as human LST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated.

Conclusions: rlst-1 is a counterpart of human LST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Anion Transport Proteins
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Cecum
  • Cholestasis / etiology
  • Cholestasis / genetics
  • Common Bile Duct
  • Feedback
  • Female
  • Gene Expression Regulation*
  • Ligation
  • Liver / metabolism*
  • Molecular Sequence Data
  • Oocytes
  • Punctures
  • RNA, Messenger / metabolism
  • Rats
  • Xenopus laevis


  • Anion Transport Proteins
  • Carrier Proteins
  • RNA, Messenger

Associated data

  • GENBANK/AF147740