2.A.17.4.4
The renal brush-border electrogenic, proton-coupled, broad specificity, high affinity, peptide transporter, PepT2 (Rubio-Aliaga et al., 2000). It is competitively inhibited by L-4,4'-Biphenylalanyl-L-Proline (Bip-Pro) with ~10-20µM affinity. Inhibitor/substrates includes cefadroxil, Ala-4-nitroanilide and delta-aminolevulinic acid (Knutter et al., 2007).  It transports the fluorescent tracer-dipeptide beta-Ala-Lys-Nepsilon-7-amino-4-methyl-coumarin-3-acetic acid (Ala-Lys-AMCA). Whole-mount preparations from mouse, rat, and guinea pig stomach and small and large intestine were incubated with Ala-Lys-AMCA in the presence or absence of the uptake-inhibitors L-histidine, D-phenylalanyl-L-alanine (D-Phe-Ala), glycyl-L-sarcosine (Gly-Sar), glycyl-L-glutamine (Gly-Gln), benzylpenicillin, and cefadroxil. Fluorescence microscopy revealed that Ala-Lys-AMCA specifically accumulated in both ganglionic layers of the enteric nervous system (ENS) in all regions and species studied (Rühl et al. 2005). This could be inhibited by Gly-Sar, D-Phe-Ala, Gly-Gln, and cefadroxil, but not by free histidine and benzylpenicillin, indicating uptake via PEPT2. Accordingly, dipeptide uptake was completely abolished in PEPT2-deficient mice.