Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2.
Article Details
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Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH
Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2.
Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308.
- PubMed ID
- 9092716 [ View in PubMed]
- Abstract
The present study was undertaken to investigate the interaction of anionic cephalosporins (cefixime, ceftibuten, and cefdinir) with the renal peptide transporter (PEPT 2) and the intestinal peptide transporter (PEPT 1) using four different experimental model systems. In the first approach, the human colon carcinoma cell line Caco-2 which expresses PEPT 1 and the SHR rat kidney cell line SKPT which expresses PEPT 2 were used. The uptake of the dipeptide Gly-Sar mediated by PEPT 1 or PEPT 2 in these cells was inhibited significantly by the anionic cephalosporins, with the following order of potency: ceftibuten > cefixime > cefdinir. The inhibition was competitive in nature. Even though the order of potency was the same for PEPT 1 and PEPT 2, PEPT 1 exhibited much lesser sensitivity to inhibition than PEPT 2. In the second approach, the cloned human PEPT 1 and PEPT 2 were functionally expressed in HeLa cells following which the cells were used to study the interaction of anionic cephalosporins with PEPT 1 and PEPT 2. Again, Gly-Sar uptake mediated by the human PEPT 1 and PEPT 2 in HeLa cells was found to be inhibited by the anionic cephalosporins with the same order potency as in Caco-2 and SKPT cells. In the third approach, brush border membrane vesicles isolated from rat kidneys were employed. In this approach also it was found that PEPT 2-mediated Gly-Sar uptake was inhibited by cefixime and ceftibuten. In the fourth approach, the human PEPT 1 was expressed in Xenopus laevis oocytes and PEPT 1-mediated transport of ceftibuten was investigated directly by electrophysiological methods. Ceftibuten evoked inward currents in PEPT 1-expressing oocytes but not in water-injected oocytes, showing that the transport of the anionic cephalosporin via PEPT 1 is associated with transfer of positive charge. The ceftibuten-evoked currents were saturable with respect to ceftibuten concentration and were markedly dependent on membrane potential. It is concluded that anionic cephalosporins interact with the peptide transporters expressed in the intestine (PEPT 1) as well as in the kidney (PEPT 2).
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cefdinir Solute carrier family 15 member 1 Protein Humans UnknownSubstrateInhibitorDetails Cefdinir Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails Cefixime Solute carrier family 15 member 1 Protein Humans UnknownSubstrateInhibitorDetails Cefixime Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails Ceftibuten Solute carrier family 15 member 1 Protein Humans UnknownSubstrateInhibitorDetails Ceftibuten Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails