Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo.
OBJECTIVE
To examine the effect of thyroid hormone status on PEPT1 in vivo, the activity and expression of PEPT1 in the small intestine were examined in euthyroid and hyperthyroid rats.


METHODS
Hyperthyroidism was induced by treating rats with L-thyroxine (12 mg/L) in the drinking water for 21 days. Transport activity was measured by everted small intestinal preparations and in situ intestinal loop technique. Expressions of PEPT1 mRNA and protein were evaluated by competitive polymerase chain reaction and Western blotting, respectively.


RESULTS
The uptake of [14C]glycylsarcosine by everted small intestinal preparations was significantly decreased in hyperthyroid rats, whereas that of methyl-alpha-D-[14C(U)]-glucopyranoside was not altered. Kinetic analysis showed that the Vmax value for [14C]glycylsarcosine uptake was significantly decreased in hyperthyroid rats, whereas the Km value was not affected. The mean portal vein concentrations after intrajejunal administration of [14C]glycylsarcosine were also decreased in hyperthyroid rats. Moreover, hyperthyroidism caused a significant decrease in the expression of PEPT1 mRNA in the small intestine, whereas the expression of Na+/glucose cotransporter (SGLT1) mRNA was not changed. The level of PEPT1 protein was also decreased in the small intestine of hyperthyroid rats.


CONCLUSIONS
These results indicate that in hyperthyroid rats, the activity and expression of PEPT1 were decreased in the small intestine.
Ashida
Kayoko
K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Katsura
Toshiya
T
Saito
Hideyuki
H
Inui
Ken-ichi
K
D000409:Alanine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D004151:Dipeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006980:Hyperthyroidism / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D007564:Japan; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics*; D008757:Methylglucosides / Q000378:metabolism / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics; D000074011:Peptide Transporter 1; D011169:Portal Vein / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051269:Sodium-Glucose Transporter 1; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology; D014316:Tritium
D002250:Carbon Radioisotopes; D004151:Dipeptides; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D027981:Symporters; C067802:intestinal peptide-proton cotransporter; D014284:Triiodothyronine; D014316:Tritium; C004194:glycylsarcosine; C027020:methylglucoside; D000409:Alanine; D013974:Thyroxine