Oral absorption of beta-lactams by intestinal peptide transport proteins

The oral p-lactams are an extremely well-absorbed class of antibiotics. They share a common uptake mechanism with small peptides for entry into the enterocyte and exit through the basolateral membrane. Transport proteins involved in the absorption of these antibiotics have been identified. Three strategies were employed to identify proteins important for the proton dependent uptake of beta-lactams. First, a 127-kDa beta-lactam transporter in rabbit intestinal brush border membranes was identified by photoaffinity labeling, protein purification and reconstitution. Second, an immunological approach resulted in the identification of HPT-1, a 120-kDa protein in apical membranes of human intestinal Caco-2 cells. The hpt-1 cDNA confers the ability to transport both cephalexin and bestatin in a proton-dependent fashion. Third, functional cloning of poly(A)(+) RNA of rabbit intestine identified a PepT1 protein that cotransports protons with small peptides, beta-lactams, and angiotensin-converting enzyme inhibitors. The kidney also expresses a transporter, PepT2, with high homology to PepT1. The expression and regulation of the intestinal transporters is reviewed. The usefulness of these transport proteins to the discovery of new oral therapeutics is discussed.