Cell Physiology

Evidence for two different broad-specific oligopeptide transporters in the intestinal cell line Caco-2 and the colonic cell line CCD841

Paresh Chothe, Nagendra Singh, Vadivel Ganapathy


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 sodium-coupled oligopeptide transporters in intestinal cell lines using the hydrolysis-resistant synthetic oligopeptides deltorphin II and 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-, though to a varying degree. The processes responsible for the uptake of deltorphin II and DADLE could be differentiated not only from their Na+-dependence but also from 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 non-opioid 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 consisting of five or more amino acids.

  • oligopeptide transport
  • intestinal cell
  • colonic epithelium
  • sodium-coupling
  • opioid peptides