Characterization of Human Orgnic Anion Transporter 4 (hOAT4) as a Low Affinity p-aminohippurate (PAH) Transporter
スポンサーリンク
概要
- 論文の詳細を見る
Organic anion transporters play an essential role in the elimination of numerous endogenous and exogenous organic anions from the body. In the present study, we investigated the transport property of human organic anion transporter 4 (hOAT4) as a p-aminohippurate (PAH) transporter. For this purpose, we established and utilized cells derived from the second segment of mice proximal tubule stably expressing hOAT4 (S2 hOAT4). RT-PCR result shows the expression of hOAT4 in S2 hOAT4. [3H] estrone sulfate (ES) and [14C] PAH uptake via hOAT4 were increased with time and concentration dependent manner. Km of ES and PAH were 9.9μM and 2.2 mM, respectively. ES uptake via hOAT4 was inhibited by PAH with competetive manner (Ki = 4.3 mM). hOAT4-mediated PAH uptake was strongly inhibited by sulfate conjugates, non-steroidal anti-inflammatory drugs, bile acids, penicillin G, BSP, probenecid, ouabain and quinidine and moderately inhibited by cAMP, cGMP and cimetidine. No inhibitory effect by tetraethylammonium and β-estradiol was observed. The present study may provide the molecular basis of drug efflux pathway in human kidneys.
著者
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Kanai Yoshikatsu
Department Of Pharmacol. Toxicol. Kyorin Univ.
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Fukutomi Toshiyuki
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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Endou Hitoshi
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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Islam Rafiqul
Department Of Host-defense Biochemistry Institute Of Tropical Medicine Nagasaki University
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Anzai Naohiko
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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FUKUTOMI Toshiyuki
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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NOSHIRO-KOFUJI Rie
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Ji JIN
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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KUNDU-SRIVASTAVA Sunena
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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MIYAO Kazuhiro
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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YAMANISHI Ai
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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