Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney

FEBS Lett. 1998 Nov 6;438(3):321-4. doi: 10.1016/s0014-5793(98)01328-3.


The functional characteristics of rat organic anion transporter OAT1 were investigated using Xenopus laevis oocytes. Uptake of p-aminohippurate (PAH) by the oocytes expressing OAT1 was markedly inhibited by glutarate, alpha-ketoglutarate and probenecid, moderately inhibited by folate and methotrexate, but not inhibited by taurocholate or tetraethylammonium. Methotrexate and folate were transported by OAT1, but probenecid, a typical inhibitor of organic anion transporter, was not transported. Inhibition of PAH uptake by aliphatic dicarboxylates with various alkyl chain lengths was maximal at 5 (glutarate) and 6 (adipate) carbon atoms. OAT1-mediated PAH uptake was markedly inhibited by phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-dibutyrate and mezerein, but not by 4alpha-phorbol 12,13-didecanoate. The inhibitory effect of PMA was attenuated in the presence of staurosporine, suggesting that OAT1 is regulated by protein kinase C. These results suggest that the substrate recognition of OAT1 is comparable to that of renal basolateral organic anion transporter, and the transport activity is regulated by protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anion Transport Proteins
  • Anions / metabolism
  • Biological Transport / drug effects
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • DNA Primers
  • DNA, Complementary
  • Dicarboxylic Acids / pharmacology
  • Diterpenes*
  • Female
  • Folic Acid / pharmacology
  • Glutarates / pharmacology
  • Kidney / metabolism*
  • Kinetics
  • Methotrexate / pharmacology
  • Oocytes / physiology
  • Phorbol Esters / pharmacology
  • Probenecid / pharmacology
  • Rats
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Staurosporine / pharmacology
  • Terpenes / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Xenopus laevis
  • p-Aminohippuric Acid / pharmacokinetics


  • Anion Transport Proteins
  • Anions
  • Carrier Proteins
  • DNA Primers
  • DNA, Complementary
  • Dicarboxylic Acids
  • Diterpenes
  • Glutarates
  • Phorbol Esters
  • Recombinant Proteins
  • Terpenes
  • mezerein
  • Folic Acid
  • Staurosporine
  • Tetradecanoylphorbol Acetate
  • Probenecid
  • p-Aminohippuric Acid
  • Methotrexate