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


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 (r2 = 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.
Naruhashi
Kazumasa
K
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Sai
Yoshimichi
Y
Tamai
Ikumi
I
Suzuki
Nagao
N
Tsuji
Akira
A
D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002434:Cefadroxil / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation / Q000502:physiology; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013217:Starvation / Q000378:metabolism*; D027981:Symporters
D002352:Carrier Proteins; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; D027981:Symporters; D002434:Cefadroxil