PEPTIDE MIMICS AS SUBSTRATES FOR THE INTESTINAL PEPTIDE TRANSPORTER

4-Aminophenylacetic acid (4-APAA), a peptide mimic lacking a peptide b ond, has been shown to interact with a proton-coupled oligopeptide tra nsporter using a number of different experimental approaches, In addit ion to inhibiting transport of labeled peptides, these studies show th at 4-APAA is itself translocated, 4-APAA transport across the rat inta ct intestine was stimulated 18-fold by luminal acidification (to pH 6. 8) as determined by high performance liquid chromatography (HPLC); in enterocytes isolated from mouse small intestine the intracellular pH w as reduced on application of 4-APAA, as shown fluorimetrically with th e pH indicator carboxy-SNARF; 4-APAA trans-stimulated radiolabeled pep tide transport in brush-border membrane vesicles isolated from rat ren al cortex; and in Xenopus oocytes expressing PepT1, 4-APAA produced tr ans-stimulation of radiolabeled peptide efflux, and as determined by H PLC, was a substrate for translocation by this transporter, These resu lts with 4-APAA show for the first time that the presence of a peptide bond is not a requirement for rapid translocation through the proton- linked oligopeptide transporter (PepT1), Further investigation will be needed to determine the minimal structural requirements for a molecul e to be a substrate for this transporter.