A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A

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  • Jutabha Promsuk
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Anzai Naohiko
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Japan
  • Hayashi Keitaro
    Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Japan
  • Domae Mariko
    Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Japan
  • Uchida Kohsuke
    Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Japan
  • Endou Hitoshi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Sakurai Hiroyuki
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan

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Abstract

In the present study, we investigated the transport of nephrotoxic mycotoxin ochratoxin A (OTxA) by a novel human organic anion transporter hNPT4 using the Xenopus oocyte expression system. hNPT4 mediated time- and concentration-dependent uptake of OTxA (Km: 802.8 μM) in a pH- and voltage-sensitive manner. Cis-inhibition experiments suggest that the substrate selectivity of hNPT4 is similar to that of hOAT4. The fact that the Km of OTxA for the efflux transporter hNPT4 was much higher than those for the uptake transporters hOAT1 and hOAT3 may favor the accumulation of OTxA in the tubular cell and lead to nephrotoxicity.

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