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Articles in PresS, published online ahead of print December 12, 2001
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00344.2001
Submitted on August 7, 2001
Accepted on December 7, 2001
1 Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
* To whom correspondence should be addressed. E-mail: inui{at}kuhp.kyoto-u.ac.jp.
The peptide 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 (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 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 [14C]
-methyl-D-glucoside and [3H]threonine uptake were not decreased. Kinetic analysis showed that T3 treatment significantly decreased the 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 glycylsarcosine by decreasing the transcription and/or stability of PEPT1 mRNA.
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