Peptide mimics as substrates for the intestinal peptide transporter.
4-Aminophenylacetic acid (4-APAA), a peptide mimic lacking a peptide bond, has been shown to interact with a proton-coupled oligopeptide transporter using a number of different experimental approaches. In addition to inhibiting transport of labeled peptides, these studies show that 4-APAA is itself translocated. 4-APAA transport across the rat intact 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 was reduced on application of 4-APAA, as shown fluorimetrically with the pH indicator carboxy-SNARF; 4-APAA trans-stimulated radiolabeled peptide transport in brush-border membrane vesicles isolated from rat renal cortex; and in Xenopus oocytes expressing PepT1, 4-APAA produced trans-stimulation of radiolabeled peptide efflux, and as determined by HPLC, was a substrate for translocation by this transporter. These results 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 molecule to be a substrate for this transporter.
Temple
C S
CS
Department of Human Anatomy, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom.
Stewart
A K
AK
Meredith
D
D
Lister
N A
NA
Morgan
K M
KM
Collier
I D
ID
Vaughan-Jones
R D
RD
Boyd
C A
CA
Bailey
P D
PD
Bronk
J R
JR
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D015820:Cadherins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D018716:Molecular Mimicry; D010648:Phenylacetates / Q000378:metabolism*; D051381:Rats; D014981:Xenopus
D000814:Aniline Compounds; D015820:Cadherins; D002352:Carrier Proteins; C490585:Cdh17 protein, mouse; C490586:Cdh17 protein, rat; D026901:Membrane Transport Proteins; D010648:Phenylacetates; C067802:intestinal peptide-proton cotransporter; C109911:4-aminophenylacetic acid