A common mechanism for transport of di- and tri-peptides by hamster jejunum in vitro.

1. This paper describes the results of a survey of the effects of peptides and amino acids on uptake by rings of everted hamster jejunum in vitro of glycylsarcosylsarcosine, a tripeptide which is taken up by an active mechanism but is very resistant to hydrolysis, appearing intact in the rings. The results of a small number of similar experiments with beta-alanylglycylglycine, another tripeptide which is taken up with very little hydrolysis, are also described. 2. Uptake of the two tripeptides was inhibited by other di- and tri-peptides, but not by free amino acids. The results suggest that dipeptides and tripeptides share a common uptake mechanism. The tetrapeptide glycylsarcosylsarcosylsarcosine did not inhibit uptake of glycylsarcosylsarcosine, and appears to be unable to utilize the uptake mechanism. 3. The results add to information about the influence of molecular structure on intestinal uptake of peptides by the system used by glycylsarcosylsarcosine, which is shared by a wide range of other di- and tri-peptides. In conjunction with previous results, they suggest that substitution of the N-terminal amino or C-terminal carboxyl groups reduces affinity for transport, that the presence of a beta-amino acid residue in a peptide is tolerated by the transport system, and that the presence of a D-amino acid residue reduces affinity for transport. Some peptides containing or made up of basic or acidic amino acid residues appear to have a low affinity for the transport system used by glycylsarcosylsarcosine. 4. Of two biologically active peptides, one, cephalexin, a peptide antibiotic, inhibited uptake of glycylsarcosylsarcosine and is probably transported by the same system. The other, prolylleucylglycineamide, which has the action of a hypothalamic regulatory factor, did not, and its structural features may make it unsuitable for carrier-mediated transport by the small intestine.