Tubular localization and drug recognition of kidney-specific organic anion transporters, OAT-K1 and OAT-K2

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

The renal proximal tubular cells play a principal role in limiting or preventing toxicity by actively secreting organic anions from the circulation into the urine. We isolated a cDNA coding a novel rat kidney specific organic anion transporter, OAT-K1, mediating transport of methotrexate (MTX). Moreover, we have isolated a new cDNA coding a rat OAT-K2, showing the 91% amino acid identity with OAT-K1. In this study, the mRNA distribution along the nephron segments and the transport characteristics of OAT-K1 and OAT-K2 have been analyzed. By the use of a reverse transcription-coupled PCR, OAT-K1 and OAT-K2 mRNAs were detected predominantly in the proximal straight tubules. When expressed in Xenopus oocytes, OAT-K1 mediated the uptake of MTX and folate, but not of taurocholate (TCA) and prostaglandin E2 (PGE2), although OAT-K2 stimulated the uptake of MTX, folate, TCA and PGE2. In stable transfectants (MDCK OAT-K1 and MDCK-OAT-K2), each transporter was localized functionally to the apical membrane and showed transport activity similar to those in the oocytes. The efflux of preloaded MTX was enhanced in both MDCK-OAT-K1 and MDCK-OAT-K2 cells. These results suggest that both OAT- K1 and OAT-K2 are apical membrane bidirectional organic anion transporters, and participate in epithelial transport of lipophilic organic anions in the kidney.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalYakugaku Zasshi
Volume120
Issue number3
DOIs
Publication statusPublished - Jan 1 2000
Externally publishedYes

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Organic Anion Transporters
Methotrexate
Kidney
Taurocholic Acid
Folic Acid
Dinoprostone
Pharmaceutical Preparations
Oocytes
Anions
Complementary DNA
Messenger RNA
Membranes
Nephrons
Xenopus
Reverse Transcription
Urine
Amino Acids
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Tubular localization and drug recognition of kidney-specific organic anion transporters, OAT-K1 and OAT-K2. / Masuda, Satohiro.

In: Yakugaku Zasshi, Vol. 120, No. 3, 01.01.2000, p. 275-281.

Research output: Contribution to journalReview article

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