Human Organic Anion Transporters Mediate the Transport of Tetracycline
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概要
- 論文の詳細を見る
The purpose of this study was to elucidate the molecular mechanism for renal tetracycline transport by human organic anion transporters (hOATs) using proximal tubular cells stably expressing hOATs. The cells stably expressing hOAT1, hOAT2, hOAT3 and hOAT4 exhibited a higher amount of [3H]tetracycline uptake compared with mock cells. The apparent Km values for hOAT2-, hOAT3- and hOAT4-mediated tetracycline uptakes were 439.9 ± 23.0, 566.2 ± 28.4 and 122.7 ± 16.0 μM, respectively. Tetracycline significantly inhibited the organic anion uptake by hOAT1, hOAT2 and hOAT4, but not hOAT3. In addition, oxytetracycline, minocycline and doxycycline inhibited the organic anion uptake by hOAT1, whereas oxytetracycline, minocycline but not doxycycline inhibited the organic anion uptake by hOAT2. In contrast, oxytetracycline, minocycline and doxycycline exhibited no significant inhibitory effects on the organic anion uptake by hOAT3 and hOAT4. HOAT1 and hOAT4 mediated the efflux of tetracycline, but hOAT2 and hOAT3 did not. These results suggest that hOAT1, hOAT2 and hOAT3 mediate the basolateral uptake and/or efflux of tetracycline, whereas hOAT4 is responsible for the reabsorption as well as the efflux of tetracycline in the apical side of the proximal tubule. These pharmacological characteristics of hOATs may be significantly related to events associated with the development of tetracycline-induced nephrotoxicity in the human kidney.
- 社団法人 日本薬理学会の論文
- 2002-01-01
著者
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Babu Ellappan
杏林大学 医学部薬理学
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Endou Hitoshi
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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Yamamoto Toshinori
昭和大学 医学部第2外科
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Yamamoto Toshinori
Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa 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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Sekine Takashi
Department Of Pediatrics Gradate School Of Medicine The University Of Tokyo
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Takeda Michio
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Cha Seok
Department Of Oral Physiology And The Second Stage Of Bk21 Chosun University College Of Dentistry
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Babu Ellappan
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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Babu Ellappan
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Endou H
Kyorin Univ. School Of Medicine Tokyo Jpn
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NARIKAWA Shinichi
Kobuchizawa Laboratories, Fuji Biomedixs Co.
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NARIKAWA Shinichi
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
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KOBAYASHI Yasuna
Department of Clinical Pharmacy, Showa University School of Pharmaceutical Sciences
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SAKTHISEKARAN Dhanapal
Department of Medical Biochemistry, University of Madras
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Yamamoto Toshinori
Clinical Pharmacy School Of Pharmaceutical Sciences Showa University
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Endou Hitoshi
Department Of Pharmacology & Toxicology Kyorin University School Of Medicine
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Sekine Takashi
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Narikawa Shinichi
Kobuchizawa Laboratories Fuji Biomedixs Co.
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Sakthisekaran Dhanapal
Department Of Medical Biochemistry Alm Postgraduate Institute Of Basic Medical Sciences University O
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Sakthisekaran Dhanapal
Department Of Medical Biochemistry University Of Madras
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Kobayashi Yasuna
Department Of Clinical Pharmacy Showa University School Of Pharmaceutical Sciences
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Yamamoto Toshinori
Department Of Clinical Pharmacy Showa University School Of Pharmaceutical Sciences
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Sekine Takashi
Department Of Applied Chemistry Tokyo Metropolitan University
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