Uptake of peptides containing Tyr-Pro by human and mouse erythrocytes

Red blood cells (RBCs) harvested from mice were used to investigate the possible existence of an uptake system for peptides in these cells. The radioactively iodinated tetrapeptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) was incubated with RBCs for varying lengths of time with or without inhibitors. The RBCs showed saturable uptake that could be inhibited by Tyr-Pro containing peptides. Uptake was also found in human RBCs, but was more robust in the mouse. Uptake by mouse RBCs was temperature dependent and magnesium sensitive but did not require sodium, potassium, or glucose. With the exception of some enkephalin- and dynorphin-related peptides that partially inhibited uptake, most substances tested were without effect. The results of HPLC showed internalization of the N-Tyr-Pro containing peptides, with accumulation of degradation products over time. The degradation products, however, did not inhibit transport, suggesting that peptides were transported intact into the RBCs with degradation occurring after internalization. This suggestion was strengthened by the finding that only the cytosol of the RBC, not its membranes, rapidly degraded Tyr-MIF-1 to free iodine and iodotyrosine. Nevertheless, the cytosol contained a large amount of immunoreactive material that eluted at the position of intact Tyr-MIF-1 on HPLC. These findings show that RBCs can take up, store, and degrade Tyr-Pro containing peptides.