ArticlePharmaceutical research1998
Overexpression of human intestinal oligopeptide transporter in mammalian cells via adenoviral transduction.
Article in Pharmaceutical research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Specific expression of proton-coupled oligopeptide transporter 1 in primary hepatocarcinoma-a novel strategy for tumor-targeted therapy.Oncology letters · 2017Article
- Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue.Molecular pharmaceutics · 2013Article
- Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach.Molecular pharmaceutics · 2011Article
- Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach.Journal of medicinal chemistry · 2010Article
- Modeling kinetics of subcellular disposition of chemicals.Chemical reviews · 2009Review
- Floxuridine amino acid ester prodrugs: enhancing Caco-2 permeability and resistance to glycosidic bond metabolism.Pharmaceutical research · 2005Article
- A fluorescent hPept1 transporter substrate for uptake screening.Pharmaceutical research · 2003Article
- Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs.Pharmaceutical research · 2002Article
- Drug inhibition of Gly-Sar uptake and hPepT1 localization using hPepT1-GFP fusion protein.AAPS pharmSci · 2001Article
- Function and immunolocalization of overexpressed human intestinal H+/peptide cotransporter in adenovirus-transduced Caco-2 cells.AAPS pharmSci · 1999Article
- Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPT1 cells overexpressing a human peptide transporter.Pharmaceutical research · 1998Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeOur goals are to establish an in vitro screening system and to evaluate a new approach in improving oral absorption of peptides and peptide-like drugs by overexpression of the human intestinal oligopeptide transporter (hPepT1). This study characterizes the expression of hPepT1 in human intestinal Caco-2 cells, rat intestinal epithelial cells (IEC-18), and human cervix epithelial cells (Hela) after adenoviral transduction.
methodsA recombinant replication-deficient adenovirus carrying the hPepT1 gene was made and used as a vector for the expression of hPepT1. The increase in the uptake permeability of cephalexin and Gly-Sar was determined. The effects of time, dose, apical pH, and substrate specificity were evaluated.
resultsA significant increase in the uptake permeability of Gly-Sar and cephalexin was found in all three cell lines after viral transduction. The increase of Gly-Sar permeability in Hela. IEC-18, and Caco-2 cells was 85-, 46-, and 15-fold respectively. Immunoblotting using an antibody against hPepT1 detected high levels of a 85-98-kDa protein in all three infected cell lines. Substrate permeability was dependent on time of infection, inward pH gradients, and multiplicity of infection (MOI). Decreased infectivity and lower hPepT1 expression were observed in differentiated Caco-2 cells. The uptake was inhibited by dipeptides and beta-lactam antibiotics but not amino acids.
conclusionsAdenoviral infected Hela cells displayed a pronounced level of hPepT1 expression with a low background and high specificity to dipeptides. These features make this system a useful tool for screening of potential substrates. The success of overexpression of hPepT1 in Caco-2 and IEC-18 cells may lead to a novel approach in improving oral absorption of peptides and peptidornimetic drugs.
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