PepT1 mRNA expression is induced by starvation and its level correlates with absorptive transport of cefadroxil longitudinally in the rat intestine

To establish how closely intestinal transport activity for beta-lactam antibiotics is correlated with PepT1 expression, absolute expression level of PepT1 mRNA and transport activity were determined longitudinally in the small intestine of fed and starved rats. For evaluation of absolute expression...

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Published in:Pharmaceutical research 2002-10, Vol.19 (10), p.1417-1423
Main Authors: NARUHASHI, Kazumasa, SAI, Yoshimichi, TAMAI, Ikumi, SUZUKI, Nagao, TSUJI, Akira
Format: Article
Language:English
Subjects:
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Biological Transport - genetics
Biological Transport - physiology
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Cefadroxil - pharmacokinetics
Gene Expression Regulation - physiology
In Vitro Techniques
Intestinal Absorption - genetics
Intestinal Absorption - physiology
Intestine, Small - metabolism
Male
Medical sciences
Peptide Transporter 1
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
RNA, Messenger - biosynthesis
Starvation - metabolism
Symporters
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Summary:To establish how closely intestinal transport activity for beta-lactam antibiotics is correlated with PepT1 expression, absolute expression level of PepT1 mRNA and transport activity were determined longitudinally in the small intestine of fed and starved rats. For evaluation of absolute expression levels of PepTl mRNA, quantitative RT-PCR by LightCycler was used. The transport function was determined by quantifying the absorptive transport of cefadroxil across intestinal tissue sheets in a Ussing chamber. PepT1 mRNA expression was highest at the lower region and lowest at the upper region in the fed rats. The value of PepT1 was about 1/5-1/6 of that of GAPDH. The expression level in the starved rats was increased in all segments, but more profoundly in the upper region. Cefadroxil transport across intestinal tissue was higher in the lower region and lower in the upper region in fed rats, and increased in the upper region in starved rats. An excellent correlation was observed between expression levels and the permeability coefficients (r2 = 0.859, p < 0.05). The intestinal transport of cefadroxil is directly proportional to PepT1 expression, suggesting that the PepT1 expression level in the rat small intestine is the major determinant of the absorption of peptide-like compounds.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1020436028194