Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats

Yuriko Shimizu, Satohiro Masuda, Kumiko Nishihara, Lin Ji, Masahiro Okuda, Ken Ichi Inui

研究成果: ジャーナルへの寄稿学術誌査読

7 被引用数 (Scopus)

抄録

In chronic renal failure (CRF), dietary protein is one of the factors that deteriorates residual renal functions. Numerous studies have indicated that the products of protein digestion are mainly absorbed as small peptides. However, how small peptides are absorbed in CRF remains poorly understood. H +-coupled peptide transporter (PEPT1/ SLC15A1) plays an important role in the absorption of small peptides and peptide-like drugs in the small intestine. Because dietary protein intake is one of the risk factors for renal failure, the alteration of intestinal PEPT1 might have implications in the progression of renal disease as well as the pharmacokinetics of peptide-like drugs. In this study, we examined the alteration of intestinal PEPT1 in 5/6 nephrectomized (5/6 NR) rats, extensively used as a model of chronic renal failure. Absorption of [14C]glycylsarcosine and ceftibuten was significantly increased in 5/6 NR rats compared with sham-operated rats, without a change in intestinal protease activity. Western blot analysis indicated that the amount of intestinal PEPT1 protein in 5/6 NR rats was increased mainly at the upper region. On the other hand, the amount of intestinal PEPT1 mRNA was not significantly different from that of sham-operated rats. These findings indicate that the increase in absorption of small peptides and peptide-like drugs, caused by the upregulation of intestinal PEPT1 protein, might contribute to the progression of renal failure as well as the alteration of drug pharmacokinetics.

本文言語英語
ページ(範囲)G664-G670
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
288
4 51-4
DOI
出版ステータス出版済み - 4月 2005

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 肝臓学
  • 消化器病学
  • 生理学(医学)

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