Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney.

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Saito H, Okuda M, Terada T, Sasaki S, Inui K

Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney.

J Pharmacol Exp Ther. 1995 Dec;275(3):1631-7.

PubMed ID

8531138 [ View in PubMed

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Abstract

A complementary DNA (cDNA) encoding the rat H+/peptide cotransporter (PepT1) was isolated, and the transport characteristics of orally active beta-lactam antibiotics were assessed by measuring uptake into Xenopus oocytes expressing the rat PepT1. The rat PepT1 cDNA encoded a 710-amino acid protein with 77% identity to the rabbit PepT1. The message for rat PepT1 was approximately 2.9 kilobases and was found predominantly in the small intestine, whereas reverse transcription-polymerase chain reaction amplification revealed that the message was expressed both in the small intestine and in the kidney cortex. The 75-kDa protein was identified by translation of in vitro synthesized transcript of rat PepT1 cDNA by use of rabbit reticulocyte lysates and by Western blot analysis with a specific antibody against the rat PepT1. When expressed in Xenopus oocytes, rat PepT1 stimulated the uptake of ceftibuten (anion) and cephradine (zwitterion) in the presence of an inward H+ gradient, and the expressed uptake was inhibited by excess dipeptides. Kinetic analysis revealed that ceftibuten has 14-fold higher affinity for the rat PepT1 than cephradine. These findings suggest that the rat PepT1 mediates H(+)-coupled uphill transport of the oral beta-lactam antibiotics across the brush-border membranes of intestinal and renal proximal tubular cells.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cefradine	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Ceftibuten	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Ubenimex	Solute carrier family 15 member 1	Protein	Humans	Unknown	Inhibitor	Details