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

Satohiro Masuda

研究成果: ジャーナルへの寄稿総説査読

2 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)275-281
ページ数7
ジャーナルYakugaku Zasshi
120
3
DOI
出版ステータス出版済み - 2000

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学

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