Pharmaceutical Research

, Volume 22, Issue 4, pp 647–660

Molecular Cloning and Functional Analyses of OAT1 and OAT3 from Cynomolgus Monkey Kidney

  • Harunobu Tahara
  • Masayuki Shono
  • Hiroyuki Kusuhara
  • Hajime Kinoshita
  • Eiichi Fuse
  • Akira Takadate
  • Masaki Otagiri
  • Yuichi Sugiyama
Research Papers

No Heading


The functional characterization of monkey OAT1 (SLC22A6) and OAT3 (SLC22A8) was carried out to elucidate species differences in the OAT1- and OAT3-mediated transport between monkey and human.


The cDNAs of monkey OAT1 and OAT3 were isolated from monkey kidney, and their stable transfectants were established in HEK293 cells (mkOAT1- and mkOAT3-HEK). Transport studies were performed using cDNA transfectants, and kinetic parameters were compared among rat, monkey and human.


The amino acid sequences of mkOAT1 and mkOAT3 exhibit 97% and 96% identity to their corresponding human orthologues. For OAT1, there was no obvious species difference in the Km values and the relative transport activities of 11 substrates with regard to p-aminohippurate transport. For OAT3, there was no species difference in the Km values and in the relative transport activities of nine substrates with regard to benzylpenicillin transport between monkey and human. However, the relative transport activities of indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, and estrone-3-sulfate showed a difference between primates and rat and gave a poor correlation.


These results suggest that monkey is a good predictor of the renal uptake of organic anions in the human.

Key words:

OAT1 OAT3 organic anion transporter species differences 















dehydroepiandrosterone sulfate








human embryonic kidney


human organic anion transporter




indoxyl sulfate


monkey organic anion transporter




nonsteroidal anti-inflammatory drugs


ochratoxin A






rat organic anion transporter


tris-buffered saline/Tween 20


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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Harunobu Tahara
    • 1
    • 2
  • Masayuki Shono
    • 1
  • Hiroyuki Kusuhara
    • 1
  • Hajime Kinoshita
    • 1
  • Eiichi Fuse
    • 2
  • Akira Takadate
    • 3
  • Masaki Otagiri
    • 4
  • Yuichi Sugiyama
    • 1
  1. 1.Graduate School of Pharmaceutical SciencesUniversity of TokyoTokyoJapan
  2. 2.Pharmaceutical Research InstituteKyowa Hakko Kogyo Co., Ltd.ShizuokaJapan
  3. 3.Daiichi College of Pharmaceutical SciencesFukuokaJapan
  4. 4.Department of Biopharmaceutics, Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan

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