Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure

Hiroki Komazawa, Hiroaki Yamaguchi, Kazuhiro Hidaka, Jiro Ogura, Masaki Kobayashi, Ken Iseki

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Chronic renal failure (CRF) leads to decreased drug renal clearance and glomerular filtration rate. However, little is known about renal tubular excretion and reabsorption in CRF. We examined transport activity of renal transporters using rats with adenine-induced CRF. We examined the effect of adenine-induced CRF on mRNA level, protein expression of transporters expressed in kidney by real-time polymerase chain reaction, and western blotting. In vivo kidney uptake clearances of benzylpenicillin and metformin, which are typical substrates for renal organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2, respectively, were evaluated. Protein and mRNA expression levels of Oat1, Oat 3, Oct1, and Oct2 were significantly decreased in adenine-induced CRF rats. On the contrary, levels of P-glycoprotein and Mdr1b mRNA were significantly increased in adenine-induced CRF rats. The mRNA expression levels of Oatp4c1, Mate1, Urat1, Octn2, and Pept1 were significantly decreased. Kidney uptake clearance of benzylpenicillin and that of metformin were significantly decreased in adenine-induced CRF rats. Also, serum from CRF rats did not affect Oat1, Oat3, Oct1, and Oct2 function. In conclusion, our results indicate that adenine-induced CRF affects renal tubular handling of drugs, especially substrates of Oat1, Oat3, Oct1, and Oct2.

Original languageEnglish
Pages (from-to)1086-1094
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume102
Issue number3
DOIs
Publication statusPublished - 2013 Mar

Keywords

  • Adenine-induced CRF
  • Distribution
  • Elimination
  • Kidney uptake clearance
  • Pharmacokinetics
  • Transport
  • Transporters

ASJC Scopus subject areas

  • Pharmaceutical Science

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