1. The intestinal transport mechanism for the tetrapeptide l-leucylglycylglycylglycine, Leu-Gly-Gly-Gly, and its relation to the transport of free Leu, Leu-Gly and Leu-Gly-Gly were investigated in vivo by means of jejunal perfusion in rats.

2. The rates of net Leu absorption from peptides (Leu-Gly and Leu-Gly-Gly-Gly) were significantly greater than those from the free amino acid mixtures when the test solutions were perfused at a concentration of 15 mmol/l.

3. Net Leu absorption rates from Leu-Gly (10 μmol/ml) and Leu-Gly-Gly (10 μmol/ml) were extensively inhibited (84% and 68% respectively) by Gly-Pro at 100 mmol/l, whereas Gly-Pro had no effect on Leu absorption from Leu-Gly-Gly-Gly. l-Alanine (Ala, 100 μmol/ml), on the other hand, which completely inhibited Leu absorption during perfusion of free Leu, inhibited Leu uptake from Leu-Gly-Gly-Gly only about 50% at all concentrations studied. Ala had no effect on Leu absorption from Leu-Gly and Leu-Gly-Gly (10 μmol/ml).

4. Neither Ala at 100 μmol/ml nor Gly-Pro at 100 μmol/ml had any effect on brush-border aminopeptidase activity in vitro, suggesting that the hydrolytic capacity of the intestinal mucosal brush border was unaltered when Ala or Gly-Pro was included in the perfusion mixture. l-Alanyl-β-naphthylamide (20 μmol/ml), which inhibited brush-border aminopeptidase activity by 85% in vitro, failed to block substantially net Leu absorption from Leu-Gly and Leu-Gly-Gly-Gly.

5. The data presented suggest that, although some of the Leu from the tetrapeptide, Leu-Gly-Gly-Gly, may be hydrolysed before transport, nearly 50% of the tetrapeptide appears to be transported intact. Although Leu-Gly, Leu-Gly-Gly and Gly-Pro seem to share a common transport mechanism, the system used for intact Leu-Gly-Gly-Gly absorption seems to be distinct. However, the present study does not exclude the possibility that binding of the tetrapeptide to the brush-border aminopeptidase alters the affinity of Leu for the amino acid carrier, and therefore further studies are necessary before firm conclusions can be made on the general mechanism of tetrapeptide transport.

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