title: Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells.
abstract: An oligopeptide transporter (PEPT1) in the small intestine plays an important role in the absorption of small peptides and peptide-like drugs. We examined the effect of thyroid hormone 3,5,3'-L-triiodothyronine (T(3)) on the activity and expression of PEPT1 in human intestinal Caco-2 cells. Treatment of Caco-2 cells with T(3) inhibited [(14)C]glycylsarcosine uptake in a time- and dose-dependent manner. [(14)C]glycylsarcosine uptake was reduced by pretreatment of the cells with 100 nM T(3) for 4 days (67% of control value), whereas methyl-alpha-D-[U-(14)C]glucopyranoside and [(3)H]threonine uptake were not decreased. Kinetic analysis showed that T(3) treatment significantly decreased the maximum uptake (V(max)) value for [(14)C]glycylsarcosine uptake but had no effect on the K(m) value. Moreover, T(3) treatment caused a significant decrease in the amount of PEPT1 mRNA (25% of the control). Western blotting indicated that the amount of PEPT1 protein in the apical membrane was decreased (70% of the control). These findings indicate that T(3) treatment inhibits the uptake of [(14)C]glycylsarcosine by decreasing the transcription and/or stability of PEPT1 mRNA.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ashida
authors.forename: Toshiya
authors.initials: T
authors.lastname: Katsura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Motohashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D004355:Drug Stability; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000032:analysis; D027981:Symporters; D013912:Threonine / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D004151:Dipeptides; D008757:Methylglucosides; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C082186:SLC15A1 protein, human; D027981:Symporters; D014284:Triiodothyronine; D014316:Tritium; C004194:glycylsarcosine; D013912:Threonine; C027020:methylglucoside