CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs.

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Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL

CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs.

J Pharm Sci. 1999 Mar;88(3):347-50.

PubMed ID

10052994 [ View in PubMed

]

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/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cefaclor	Solute carrier family 15 member 1	Protein	Humans	Unknown	Inhibitor	Details
Cefradine	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Cephalexin	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Enalapril	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Levodopa	Solute carrier family 15 member 1	Protein	Humans	Unknown	Inhibitor	Details
Methyldopa	Solute carrier family 15 member 1	Protein	Humans	Unknown	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cefaclor	Solute carrier family 15 member 1	IC 50 (nM)	8200000	N/A	N/A	Details
Cefradine	Solute carrier family 15 member 1	IC 50 (nM)	15300000	N/A	N/A	Details
Cephalexin	Solute carrier family 15 member 1	IC 50 (nM)	13700000	N/A	N/A	Details
Enalapril	Solute carrier family 15 member 1	IC 50 (nM)	4500000	N/A	N/A	Details
Levodopa	Solute carrier family 15 member 1	IC 50 (nM)	141200000	N/A	N/A	Details
Methyldopa	Solute carrier family 15 member 1	IC 50 (nM)	151600000	N/A	N/A	Details