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Am J Physiol Gastrointest Liver Physiol 282: G617-G623, 2002. First published December 12, 2001; doi:10.1152/ajpgi.00344.2001
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Vol. 282, Issue 4, G617-G623, April 2002

Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells

Kayoko Ashida, Toshiya Katsura, Hideyuki Motohashi, Hideyuki Saito, and Ken-Ichi Inui

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

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 (T3) on the activity and expression of PEPT1 in human intestinal Caco-2 cells. Treatment of Caco-2 cells with T3 inhibited [14C]glycylsarcosine uptake in a time- and dose-dependent manner. [14C]glycylsarcosine uptake was reduced by pretreatment of the cells with 100 nM T3 for 4 days (67% of control value), whereas methyl-alpha -D-[U-14C]glucopyranoside and [3H]threonine uptake were not decreased. Kinetic analysis showed that T3 treatment significantly decreased the maximum uptake (Vmax) value for [14C]glycylsarcosine uptake but had no effect on the Km value. Moreover, T3 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 T3 treatment inhibits the uptake of [14C]glycylsarcosine by decreasing the transcription and/or stability of PEPT1 mRNA.

intestinal absorption; intestinal oligopeptide transporter; hormonal regulation; gene expression


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