Pflügers Archiv

, Volume 443, Issue 2, pp 188–195

Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3

  • Valentino Cattori
  • Jessica E. Montfoort
  • Bruno Stieger
  • Lukas Landmann
  • Dirk K. Meijer
  • Kaspar H. Winterhalter
  • Peter J. Meier
  • Bruno Hagenbuch
Original Article

DOI: 10.1007/s004240100697

Cite this article as:
Cattori, V., Montfoort, J.E., Stieger, B. et al. Pflügers Arch - Eur J Physiol (2001) 443: 188. doi:10.1007/s004240100697

Abstract

Organic anion transporting polypeptides (rodents: Oatps; human: OATPs) are involved in the absorption and elimination of a wide variety of structurally unrelated amphipathic organic compounds. Several members of this protein family mediate the uptake of substrates across the basolateral membrane of hepatocytes as the first step in hepatic elimination. In contrast to the well-characterized Oatp1 and Oatp2, the localization and substrate specificity of the recently cloned Oatp4 have not been investigated in detail. Therefore, we raised an antibody against the C-terminal end of Oatp4 and localized this 85-kDa protein to the basolateral membrane of rat hepatocytes. Similar to Oatp1 and Oatp2, Oatp4 is a multispecific transporter with high affinities for bromosulfophthalein, dehydroepiandrosterone sulfate, leukotriene C4, and anionic peptides. In addition, we compared the substrate specificity of Oatp4 to that of Oatp3, which so far has mainly been shown to mediate intestinal bile acid transport. Oatp3 had a similar broad substrate specificity, but in general much lower affinities than Oatp4. Thus, while Oatp4 seems to work in concert with Oatp1 and Oatp2 in the basolateral membrane of rat hepatocytes, Oatp3 is a multispecific transport system in the small intestine.

Anions/pharmacokinetics Biological transport/physiology Liver Organic anion transporting polypeptides 

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Valentino Cattori
    • 1
  • Jessica E. Montfoort
    • 1
  • Bruno Stieger
    • 1
  • Lukas Landmann
    • 3
  • Dirk K. Meijer
    • 4
  • Kaspar H. Winterhalter
    • 2
  • Peter J. Meier
    • 1
  • Bruno Hagenbuch
    • 1
  1. 1.Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, 8091 ZurichSwitzerland
  2. 2.Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), CH-8092 ZurichSwitzerland
  3. 3.Institute of Anatomy, University of Basel, 4056 BaselSwitzerland
  4. 4.Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration, 9713 AW GroningenThe Netherlands