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.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D003864:Depression, Chemical; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006033:Glycylglycine / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
D000596:Amino Acids; D006033:Glycylglycine; D004744:Enkephalin, Methionine; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone