Human Organic Anion Transporters Mediate the Transport of Tetracycline.

• Babu Ellappan

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Takeda Michio

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Narikawa Shinichi

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Kobayashi Yasuna

  Department of Clinical Pharmacy, Showa University School of Pharmaceutical Sciences

• Yamamoto Toshinori

  Department of Clinical Pharmacy, Showa University School of Pharmaceutical Sciences

• Cha Seok Ho

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Sekine Takashi

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Sakthisekaran Dhanapal

  Department of Medical Biochemistry, University of Madras

• Endou Hitoshi

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

抄録

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 K_m 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.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 88 (1), 69-76, 2002

  公益社団法人 日本薬理学会

キーワード

• Tetracycline
• Organic anion transporter
• Proximal tubule
• Transport
• Cell line

詳細情報

• CRID: 1390001204286187392
• NII論文ID: 10007944778
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.88.69
• COI: 1:STN:280:DC%2BD387itFKmsw%3D%3D
• ISSN: 13473506
• ISSN: 00215198
• ISSN: http://id.crossref.org/issn/00215198
• NDL書誌ID: 6054616
• PubMed: 11855680
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6054616
• Web Site: https://api.elsevier.com/content/article/PII:S002151981930232X?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S002151981930232X?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2002166514
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可