A brain-to-blood carrier-mediated transport system for small, N-tyrosinated peptides

Recently, we found that lipophilicity is a good predictor of the degree to which most peptides cross the blood-brain-barrier. Small (MW less than 1000) peptides with an N-terminal tyrosine, however, penetrated to a much smaller degree than was predicted by their measurements of lipophilicity. We show here that two such peptides, N-Tyr-MIF-1 and Met-enkephalin, can significantly inhibit transport of 125I-N-Tyr-MIF-1 out of the rat brain in vivo in a saturable, dose-dependent way. The half-time disappearance of injected 125I-N-Tyr-MIF-1 from the rat brain was 12.4 min but when injected with 200 nmol/animal of unlabeled N-Tyr-MIF-1 was 23.6 min (p less than 0.01). The Km was calculated to be 0.123 nmol. At higher doses, leucine, but not tyrosine, alanine, glutamine, MIF-1, or the dipeptide Gly-Gly, also significantly inhibited transport out of the brain.