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

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

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 aject the membrane localization and functional characteristics; 50 kDa with multispecificity in the apical membrane ofMDCK 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 5W6 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.

Original languageEnglish
Pages (from-to)91-103
Number of pages13
JournalDrug metabolism and pharmacokinetics
Volume18
Issue number2
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

Fingerprint

Organic Anion Transporters
Methotrexate
Pharmacokinetics
LLC-PK1 Cells
Kidney
Membranes
Pharmaceutical Preparations
Leucovorin
Microvilli
Organism Cloning
Complementary DNA
Cell Membrane
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

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abstract = "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 aject the membrane localization and functional characteristics; 50 kDa with multispecificity in the apical membrane ofMDCK 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 5W6 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.",
author = "Satohiro Masuda",
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AB - 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 aject the membrane localization and functional characteristics; 50 kDa with multispecificity in the apical membrane ofMDCK 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 5W6 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.

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