Review: Functional characteristics and pharmacokinetic significance of kidney-specific organic anion transporters, OAT-K1 and OAT-K2, in the urinary excretion of anionic drugs

• MASUDA Satohiro

  Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

書誌事項

タイトル別名

• Functional Characteristics and Pharmacokinetic Significance of Kidney-specific Organic Anion Transporters, OAT-K1 and OAT-K2, in the Urinary Excretion of Anionic Drugs

抄録

During the last decade, cDNA cloning has identified various gene families of drug transporters, and pharmacokinetic studies of drugs based on the molecular characteristics of transporters have advanced. We cloned and characterized two organic anion transporters OAT-K1 and OAT-K2 from the rat kidney. The expression of both transporters was limited to the kidney, especially the brush-border membranes of proximal tubules, with an apparent molecular mass of 40 kDa. Using MDCK or LLC-PK1 cells stably expressing OAT-K1, posttranslational cleavage was suggested to affect the membrane localization and functional characteristics; 50 kDa with multispecificity in the apical membrane of MDCK cells and 70 kDa with methotrexate specific transport in the basolateral membrane of LLC-PK1 cells. A wide variety of anionic compounds including methotrexate are bidirectionally transported via OAT-K1 and OAT-K2 across the apical membrane in the MDCK-transfectants. The urinary secretion of methotrexate was depressed in 5/6 nephrectomized rats in association with the selective loss of OAT-K1 and OAT-K2 expression, and both transporters were suggested to be target molecules for methotrexate-folinic acid rescue. In this review, recent advances in the study of OAT-K1 and OAT-K2 were summarized in comparison with other transporters.

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 18 (2), 91-103, 2003

  日本薬物動態学会

キーワード

• nephron
• brush-border membrane
• renal failure
• methotrexate
• folinic acid rescue
• pathophysiological role

詳細情報

• CRID: 1390001205178649216
• NII論文ID: 10011238327
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.18.91
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715308697?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715308697?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2004005549
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可