Regulation of the oligopeptide transporter, PEPT-1, in DSS-induced rat colitis.
The effect of colitis induced with dextran sodium sulfate (DSS) in rats on the bioavailability of drugs transported by the oligopeptide transporter PepT-1 was analyzed by studying the pharmacokinetics of PepT-1 substrates: cephalexin and valacyclovir, the prodrug of antiviral acyclovir. Western blot, immunohistochemistry, and real-time PCR were used to determine the PepT-1 protein and gene expression. We observed (1) no significant modification of PepT-1 expression in the duodenum and jejunum; (2) a slight decrease in both PepT-1 mRNA (50%) and protein expression (25%) in the ileum following DSS challenge; and (3) ectopic PepT-1 immunostaining in regenerative hyperplasia segments in the distal colon from DSS-treated rats where focal inflammation is localized. However, no modification of pharmacokinetic parameters (C (max), T (max), AUC) of cephalexin or acyclovir was detected. In conclusion, DSS-induced rat colitis did not alter PepT-1 substrate bioavailability despite certain modifications in PepT-1 expression profile.
Radeva
Genia
G
UPRES 2706, Faculté de Pharmacie Paris Sud, Laboratoire de Pharmacie Clinique, 5 rue Jean Baptiste Clément, 92296, Chatenay-Malabry, France.
Buyse
Marion
M
Hindlet
Patrick
P
Beaufils
Benjamin
B
Walker
Francine
F
Bado
André
A
Farinotti
Robert
R
D000212:Acyclovir / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000493:pharmacokinetics; D001682:Biological Availability; D002506:Cephalexin / Q000493:pharmacokinetics; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism*; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; D027981:Symporters; D014633:Valine; D000077483:Valacyclovir; D002506:Cephalexin; D000212:Acyclovir