H. Tanaka et al., REGULATION OF THE PEPT1 PEPTIDE TRANSPORTER IN THE RAT SMALL-INTESTINE IN RESPONSE TO 5-FLUOROURACIL-INDUCED INJURY, Gastroenterology, 114(4), 1998, pp. 714-723
Background & Aims: The oligopeptide transport system of the small inte
stine is resistant to mucosal injury. The mechanism of this resistance
was investigated by examining the activity level and expression of th
e peptide transporter PepT1 in the intestine of rats treated with 5-fl
uorouracil. Methods: The expression and localization of PepT1 were exa
mined by immunoblot analysis of brush border membrane vesicles and imm
unohistochemical analysis of intestinal sections with PepT1-specific r
abbit polyclonal antibodies. Also, Northern blot analysis was used for
the expression of PepT1 messenger RNA (mRNA). Results: Although the a
mounts of sucrase and an Na+-dependent glucose transporter protein in
intestinal vesicles decreased markedly after 5-fluorouracil treatment,
the amount of PepT1 protein remained largely unaffected. Immunohistoc
hemical analysis also showed that the PepT1 immunoreactivity level was
preserved in the brush border membrane of the remaining villi of 5-fl
uorouracil-treated rats. Levels of amino acid, glucose, and phosphate
transporter mRNAs were profoundly depressed in 5-fluorouracil-treated
animals, whereas the level of PepT1 mRNA conversely increased. Conclus
ions: The resistance of intestinal peptide transport to tissue injury
may be attributable to increased synthesis of PepT1 rather than to a c
hange in the kinetic properties of the residual absorbing cells.