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

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

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...

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Main Authors: Promsuk Jutabha, Naohiko Anzai, Keitaro Hayashi, Mariko Domae, Kohsuke Uchida, Hitoshi Endou, Hiroyuki Sakurai
Format: Article
Language:English
Published: Elsevier 2011-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319306796
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spelling doaj-942cca8f029c41d3b09025d93dad73e82020-11-25T02:37:28ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-011164392396A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin APromsuk Jutabha0Naohiko Anzai1Keitaro Hayashi2Mariko Domae3Kohsuke Uchida4Hitoshi Endou5Hiroyuki Sakurai6Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan; Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, Japan; Corresponding author (affiliation #2). anzai@dokkyomed.ac.jpDepartment of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, JapanDepartment of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, JapanDepartment of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi 321-0293, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanAbstract.: 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. Keywords:: ochratoxin A, organic anion transporter, nephrotoxicityhttp://www.sciencedirect.com/science/article/pii/S1347861319306796
collection DOAJ
language English
format Article
sources DOAJ
author Promsuk Jutabha
Naohiko Anzai
Keitaro Hayashi
Mariko Domae
Kohsuke Uchida
Hitoshi Endou
Hiroyuki Sakurai
spellingShingle Promsuk Jutabha
Naohiko Anzai
Keitaro Hayashi
Mariko Domae
Kohsuke Uchida
Hitoshi Endou
Hiroyuki Sakurai
A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
Journal of Pharmacological Sciences
author_facet Promsuk Jutabha
Naohiko Anzai
Keitaro Hayashi
Mariko Domae
Kohsuke Uchida
Hitoshi Endou
Hiroyuki Sakurai
author_sort Promsuk Jutabha
title A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
title_short A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
title_full A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
title_fullStr A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
title_full_unstemmed A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A
title_sort novel human organic anion transporter npt4 mediates the transport of ochratoxin a
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2011-01-01
description 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. Keywords:: ochratoxin A, organic anion transporter, nephrotoxicity
url http://www.sciencedirect.com/science/article/pii/S1347861319306796
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