Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury.
OBJECTIVE
The oligopeptide transport system of the small intestine is resistant to mucosal injury. The mechanism of this resistance was investigated by examining the activity level and expression of the peptide transporter PepT1 in the intestine of rats treated with 5-fluorouracil.


METHODS
The expression and localization of PepT1 were examined by immunoblot analysis of brush border membrane vesicles and immunohistochemical analysis of intestinal sections with PepT1-specific rabbit polyclonal antibodies. Also, Northern blot analysis was used for the expression of PepT1 messenger RNA (mRNA).


RESULTS
Although the amounts 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. Immunohistochemical analysis also showed that the PepT1 immunoreactivity level was preserved in the brush border membrane of the remaining villi of 5-fluorouracil-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.


CONCLUSIONS
The resistance of intestinal peptide transport to tissue injury may be attributable to increased synthesis of PepT1 rather than to a change in the kinetic properties of the residual absorbing cells.
Tanaka
H
H
Department of Clinical Nutrition, School of Medicine, Tokushima University, Tokushima, Japan.
Miyamoto
K I
KI
Morita
K
K
Haga
H
H
Segawa
H
H
Shiraga
T
T
Fujioka
A
A
Kouda
T
T
Taketani
Y
Y
Hisano
S
S
Fukui
Y
Y
Kitagawa
K
K
Takeda
E
E
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005472:Fluorouracil / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013393:Sucrase / Q000378:metabolism; D027981:Symporters
D002352:Carrier Proteins; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; D027981:Symporters; D013393:Sucrase; D005947:Glucose; D005998:Glycine; D005472:Fluorouracil