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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number4 51-4
DOIs
Publication statusPublished - Apr 1 2005

Fingerprint

Up-Regulation
Peptides
Proteins
Chronic Kidney Failure
Dietary Proteins
Pharmaceutical Preparations
Renal Insufficiency
Pharmacokinetics
Kidney
ceftibuten
glycylsarcosine
Proteolysis
Small Intestine
Disease Progression
Peptide Hydrolases
Western Blotting
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats. / Shimizu, Yuriko; Masuda, Satohiro; Nishihara, Kumiko; Ji, Lin; Okuda, Masahiro; Inui, Ken Ichi.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 4 51-4, 01.04.2005.

Research output: Contribution to journalArticle

@article{f4a5e09df3414fe484d2e36d0e5b566a,
title = "Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats",
abstract = "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.",
author = "Yuriko Shimizu and Satohiro Masuda and Kumiko Nishihara and Lin Ji and Masahiro Okuda and Inui, {Ken Ichi}",
year = "2005",
month = "4",
day = "1",
doi = "10.1152/ajpgi.00270.2004",
language = "English",
volume = "288",
journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "4 51-4",

}

TY - JOUR

T1 - Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats

AU - Shimizu, Yuriko

AU - Masuda, Satohiro

AU - Nishihara, Kumiko

AU - Ji, Lin

AU - Okuda, Masahiro

AU - Inui, Ken Ichi

PY - 2005/4/1

Y1 - 2005/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=15244362567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15244362567&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00270.2004

DO - 10.1152/ajpgi.00270.2004

M3 - Article

VL - 288

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 4 51-4

ER -