Cell Biochemistry and Biophysics

, Volume 36, Issue 2–3, pp 169–174 | Cite as

Molecular characterization of the renal organic anion transporter 1

  • Gerhard Burckhardt
  • Natascha A. Wolff
  • Andrew Bahn
Review Article

Abstract

Organic anions of diverse chemical structures are secreted in renal proximal tubules. The first step in secretion, uptake of organic anions across the basolateral membrane of tubule cells, is mediated for the polyspecific organic anion transporter 1 (OAT1), which exchanges extracellular organic anions for intracellular α-ketoglutarate or glutarate. OAT1 orthologs cloned from various species show 12 putative transmembrane domains and possess several sites for potential post-translational modification. The gene for the human OAT1 is located on chromosome 11q13.1 and is composed of 10 exons. Alternative splicing within exon 9 gives rise to four variants, two of which (OAT1-1 and OAT1-2) are functional. Following heterologous expression in Xenopus laevis oocytes, flounder renal OAT1 transported p-aminohippurate, glutarate, several diuretics, and the nephrotoxic agent ochratoxin A. Two cationic amino acid residues, lysine 394 and arginine 478, were found to be important for interaction with glutarate. Anionic neurotransmitter metabolites and the heavy-metal chelator, 2,3-dimercaptopropane sulfonate, interacted with the rabbit renal OAT1, which is expressed in kidneys and the retina.

Index Entries

Kidney proximal tubule anion secretion organic anions p-aminohippurate OAT1 anion exchanger 

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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Gerhard Burckhardt
    • 1
  • Natascha A. Wolff
    • 1
  • Andrew Bahn
    • 1
  1. 1.Institute of PhysiologyGeorg-August UniversityGöttingenGermany

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