CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs
Abstract
The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO-K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. Vmax in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO-K1 cells, while Km values were similar in all cases. The uptake of beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO-K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEP…
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- Authors
- Han, H.-K., Rhie, J. K., Oh, D.-M., Saito, G., Hsu, C.-P., Stewart, B. H., & Amidon, G. L.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Amidon, Gordon L.
- ORCID
- Amidon, Gordon L.
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- American Geophysical Union (AGU)
- Published
- 1999-03
- Volume
- 88
- Issue
- 3
- Pages
- 347-350
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2155020314
- Cited by
- 42
- References
- 0
- Citations by year
- 2016: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 37188, R01GM037188)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- hPEPT1, peptide transporters, beta-lactam antibiotics, enalapril, amino acid transporters, transporter inhibition, Caco-2 cells
- MeSH terms
- Peptide Transporter 1, Animals, Biological Transport, Carrier Proteins, Dipeptides, Cricetinae, Humans, Kinetics, Transfection, Reproducibility of Results, CHO Cells, Caco-2 Cells, Symporters
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