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PepT1 mRNA Expression Is Induced by Starvation and Its Level Correlates with Absorptive Transport of Cefadroxil Longitudinally in the Rat Intestine

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Abstract

Purpose. 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.

Methods. For evaluation of absolute expression levels of PepT1 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.

Results. 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 (r 2= 0.859, p < 0.05).

Conclusions. 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.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, 920-0934, Japan

    Kazumasa Naruhashi, Yoshimichi Sai, Ikumi Tamai, Nagao Suzuki & Akira Tsuji

  2. CREST, Japan Science and Technology Corporation, 4-1-8 Moto-machi, Kawaguchi, 332-0012, Japan

    Akira Tsuji

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  1. Kazumasa Naruhashi
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  2. Yoshimichi Sai
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  3. Ikumi Tamai
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Correspondence to Akira Tsuji.

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Naruhashi, K., Sai, Y., Tamai, I. et al. PepT1 mRNA Expression Is Induced by Starvation and Its Level Correlates with Absorptive Transport of Cefadroxil Longitudinally in the Rat Intestine. Pharm Res 19, 1417–1423 (2002). https://doi.org/10.1023/A:1020436028194

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