TY - JOUR
T1 - Evidence for two different broad-specificity oligopeptide transporters in intestinal cell line caco-2 and colonic cell line CCD841
AU - Chothe, Paresh
AU - Singh, Nagendra
AU - Ganapathy, Vadivel
PY - 2011/6/2
Y1 - 2011/6/2
N2 - Recently the existence of two different Na+-coupled oligopeptide transport systems has been described in mammalian cells. These transport systems are distinct from the previously known H+/peptide cotransporters PEPT1 and PEPT2, which transport only dipeptides and tripeptides. To date, the only peptide transport system known to exist in the intestine is PEPT1. Here we investigated the expression of the Na+-coupled oligopeptide transporters in intestinal cell lines, using the hydrolysis-resistant synthetic oligopeptides deltorphin II and [D-Ala2,D-Leu5]enkephalin (DADLE) as model substrates. Caco-2 cells and CCD841 cells, both representing epithelial cells from human intestinal tract, were able to take up these oligopeptides. Uptake of deltorphin II was mostly Na+ dependent, with more than 2 Na+ involved in the uptake process. In contrast, DADLE uptake was only partially Na+ dependent. The uptake of both peptides was also influenced by H+ and Cl-, although to a varying degree. The processes responsible for the uptake of deltorphin II and DADLE could be differentiated not only by their Na+ dependence but also by their modulation by small peptides. Several dipeptides and tripeptides stimulated deltorphin II uptake but inhibited DADLE uptake. These modulating small peptides were, however, not transportable substrates for the transport systems that mediate deltorphin II or DADLE uptake. These two oligopeptide transport systems were also able to take up several nonopioid oligopeptides, consisting of 9-17 amino acids. This represents the first report on the existence of transport systems in intestinal cells that are distinct from PEPT1 and capable of transporting oligopeptides consistingof five or more amino acids.
AB - Recently the existence of two different Na+-coupled oligopeptide transport systems has been described in mammalian cells. These transport systems are distinct from the previously known H+/peptide cotransporters PEPT1 and PEPT2, which transport only dipeptides and tripeptides. To date, the only peptide transport system known to exist in the intestine is PEPT1. Here we investigated the expression of the Na+-coupled oligopeptide transporters in intestinal cell lines, using the hydrolysis-resistant synthetic oligopeptides deltorphin II and [D-Ala2,D-Leu5]enkephalin (DADLE) as model substrates. Caco-2 cells and CCD841 cells, both representing epithelial cells from human intestinal tract, were able to take up these oligopeptides. Uptake of deltorphin II was mostly Na+ dependent, with more than 2 Na+ involved in the uptake process. In contrast, DADLE uptake was only partially Na+ dependent. The uptake of both peptides was also influenced by H+ and Cl-, although to a varying degree. The processes responsible for the uptake of deltorphin II and DADLE could be differentiated not only by their Na+ dependence but also by their modulation by small peptides. Several dipeptides and tripeptides stimulated deltorphin II uptake but inhibited DADLE uptake. These modulating small peptides were, however, not transportable substrates for the transport systems that mediate deltorphin II or DADLE uptake. These two oligopeptide transport systems were also able to take up several nonopioid oligopeptides, consisting of 9-17 amino acids. This represents the first report on the existence of transport systems in intestinal cells that are distinct from PEPT1 and capable of transporting oligopeptides consistingof five or more amino acids.
KW - Colonic epithelium
KW - Opioid peptides
KW - Sodium coupling
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U2 - 10.1152/ajpcell.00299.2010
DO - 10.1152/ajpcell.00299.2010
M3 - Article
C2 - 21307350
AN - SCOPUS:79957667487
SN - 0363-6143
VL - 300
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 6
ER -