Prediction of glycylsarcosine transport in Caco-2 cell lines expressing PEPT1 at different levels

H(+)-coupled peptide transporter 1 (PEPT1) and the basolateral peptide transporter mediate the absorption of small peptides and peptide-like drugs in the small intestine. Recently, we constructed a mathematical model to simulate glycylsarcosine (Gly-Sar) transport in Caco-2 cells. In this study, we...

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Bibliographic Details
Published in:Pflügers Archiv 2006-04, Vol.452 (1), p.64-70
Main Authors: Irie, Megumi, Terada, Tomohiro, Tsuda, Masahiro, Katsura, Toshiya, Inui, Ken-Ichi
Format: Article
Language:English
Subjects:
Biological Transport - physiology
Caco-2 Cells
Carbon Radioisotopes
Cells
Computer Simulation
Dipeptides - metabolism
Epithelium - metabolism
Gene Expression
Humans
Kinetics
Models, Biological
Peptide Transporter 1
Peptides
RNA, Messenger - metabolism
Symporters - metabolism
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Summary:H(+)-coupled peptide transporter 1 (PEPT1) and the basolateral peptide transporter mediate the absorption of small peptides and peptide-like drugs in the small intestine. Recently, we constructed a mathematical model to simulate glycylsarcosine (Gly-Sar) transport in Caco-2 cells. In this study, we attempted to adjust our model to a change in the expression level of PEPT1. To obtain cell lines expressing PEPT1 at different levels, recloning of Caco-2 cells was performed, and nine clones were isolated. Compared with parental cells, clones 1 and 9 exhibited the lowest and the highest levels of [(14)C]Gly-Sar uptake from the apical side, respectively, whereas activities of the basolateral peptide transporter were comparable. Kinetic analysis demonstrated that the difference in the activity of PEPT1 was accounted by variations in V (max). Moreover, PEPT1 mRNA level was positively related to the activity of [(14)C]Gly-Sar uptake (r=0.55). Based on these findings, the V (max) value of PEPT1 was defined as a variable using the amount of PEPT1 mRNA as an index of the expression level. With this improved model, Gly-Sar transport in clones 1 and 9 was well-predicted, suggesting that our model can simulate Gly-Sar transport in cells expressing PEPT1 at different levels.
ISSN:0031-6768
1432-2013
DOI:10.1007/s00424-005-0005-x