Human Organic Anion Transporter 4 Is a Renal Apical Organic Anion/Dicarboxylate Exchanger in the Proximal Tubules
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概要
- 論文の詳細を見る
Human organic anion transporter OAT4 is expressed in the kidney and placenta and mediates high-affinity transport of estrone-3-sulfate (E1S). Because a previous study demonstrated no trans-stimulatory effects by E1S, the mode of organic anion transport via OAT4 remains still unclear. In the present study, we examined the driving force of OAT4 using mouse proximal tubular cells stably expressing OAT4 (S2 OAT4). OAT4-mediated E1S uptake was inhibited by glutarate (GA) (IC50: 1.25 mM) and [14C]GA uptake via S2 OAT4 was significantly trans-stimulated by unlabeled GA (5 mM) (P<0.001). [3H]E1S uptake via S2 OAT4 was significantly trans-stimulated by preloaded GA (P<0.001) and its [14C]GA efflux was significantly trans-stimulated by unlabeled E1S in the medium (P<0.05). In additon, both the uptake and efflux of [14C]p-aminohippuric acid (PAH) and [14C]GA via S2 OAT4 were significantly trans-stimulated by unlabeled GA or PAH. The immunoreactivities of OAT4 were observed in the apical membrane of proximal tubules along with those of basolateral organic anion/dicarboxylate exchangers such as hOAT1 and hOAT3 in the same tubular population. These results indicate that OAT4 is an apical organic anion/dicarboxylate exchanger and mainly functions as an apical pathway for the reabsorption of some organic anions in renal proximal tubules driven by an outwardly directed dicarboxylate gradient.
- 社団法人 日本薬理学会の論文
- 2004-03-01
著者
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Endou Hitoshi
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Anzai Naohiko
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Takeda Michio
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
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KANAI Yoshikatsu
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Jutabha Promsuk
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Jutabha Promsuk
杏林大学 医学部薬理学
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Sophasan Samaisukh
杏林大学 医学部薬理学教室
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Sophasan Samaisukh
Department Of Physiology Faculty Of Science Mahidol University
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Sophasan Samaisukh
Department Of Physiology Faculty Of Sciences Mahidol University
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Endou Hitoshi
群馬大学 医学系研究科病態制御内科学
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Endou Hitoshi
杏林大学 医学部薬理学教室
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Takeda Michio
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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MIYAZAKI Hiroki
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences
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NOSHIRO Rie
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Tsuda Minoru
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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EKARATANAWONG Sophapun
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Kanai Yoshikatsu
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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Kanai Yoshikatsu
Department Of Pharmacol. Toxicol. Kyorin Univ.
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Ekaratanawong Sophapun
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Endou Hitoshi
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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Noshiro Rie
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Kanai Yoshikatsu
Division Of Bio-system Pharmacology Department Of Pharmacology Osaka University Graduate School Of M
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Miyazaki Hiroki
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Miyazaki Hiroki
Department Of Mechanical Engineering Kinki University
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Takeda M
Pharmaceutical Laboratory Sanwa Kagaku Kenkyusho Co. Ltd
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Anzai Naohiko
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Jutabha Promsuk
Department Of Pharmacology And Toxicology Dokkyo Medical University School Of Medicine
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Miyazaki Hiroki
Department of Internal Medicine, University of Tokyo
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