Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter

Xiao Yan Chu, Gloria P. Sánchez-Castaño, Kazutaka Higaki, Doo Man Oh, Cheng Pang Hsu, Gordon L. Amidon

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The proton-coupled oligopeptide transporter (PEPT1) has been shown to mediate mucosal cell transport of di- and tripeptide, and some peptidomimetic drugs. In this study, we determined the correlation between PEPT1 protein expression and the permeability of cephalexin, a substrate of PEPT1, in human PEPT1 (hPEPT1)-overexpressed Caco-2 cells (Caco-2/hPEPT1 cells) and rat jejunum. Caco-2/hPEPT1 cells with various levels of hPEPT1 expression were established by an adenoviral transfection system. The effective intestinal permeability (Peff) in rat jejunum was evaluated using a single pass in situ perfusion method. The level of PEPT1 in Caco-2/hPEPT1 cells and rat intestinal mucosal samples was quantitated by densitometry after immunoblotting and enhanced chemiluminescence detection. In Caco-2/hPEPT1 cells, an excellent correlation was observed between cephalexin uptake and hPEPT1 expression (R2 = 0.96, P <0.005). This demonstrates that cephalexin uptake is directly proportional to hPEPT1 expression. In the rat perfusion study, the mean Peff ± S.D. (n = 15) of cephalexin was 3.89 ± 1.63 × 10-5 cm/s. A very significant correlation between PEPT1 expression and cephalexin permeability with an R2 = 0.63 (P <0.001) was observed. This indicates that the variation in PEPT1 expression is one of the major factors accounting for variable intestinal cephalexin absorption. To our knowledge, this is the most direct evidence that variation of PEPT1 expression is correlated with absorption permeability variation of peptide-like compounds in vitro and in vivo.

Original languageEnglish
Pages (from-to)575-582
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume299
Issue number2
Publication statusPublished - 2001
Externally publishedYes

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Cephalexin
Oligopeptides
Permeability
Epithelial Cells
Jejunum
Perfusion
Peptidomimetics
Caco-2 Cells
Densitometry
Dipeptides
Intestinal Absorption
Luminescence
Immunoblotting
Transfection
Protons
Peptides

ASJC Scopus subject areas

  • Pharmacology

Cite this

Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. / Chu, Xiao Yan; Sánchez-Castaño, Gloria P.; Higaki, Kazutaka; Oh, Doo Man; Hsu, Cheng Pang; Amidon, Gordon L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 299, No. 2, 2001, p. 575-582.

Research output: Contribution to journalArticle

Chu, Xiao Yan ; Sánchez-Castaño, Gloria P. ; Higaki, Kazutaka ; Oh, Doo Man ; Hsu, Cheng Pang ; Amidon, Gordon L. / Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. In: Journal of Pharmacology and Experimental Therapeutics. 2001 ; Vol. 299, No. 2. pp. 575-582.
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