Blood-brain barrier restriction of peptides and the low uptake of enkephalins.

Blood-brain barrier penetration of leucine-enkephalin, methionine-enkephalin, and other peptide-like compounds was measured after intracarotid injection of three isotopes and was found to be non-saturable over the nanomolar range of concentrations tested. No significant differences in brain regional extraction of leucine enkephalin (or morphine or heroin) were observed. In contrast to previous reports, the brain extraction of enkephalins was minimally low (E = 2-3%) and about the same order of magnitude as other putative neurotransmitters. Brain extractions of other peptide-like compounds were similarly small: TRH, E = 1%; glutathione, E = 0.5%; beta-alanyl histidine, E = 1%; and thioacetyl coenzyme A, E = 2%. Extraction of the non-diffusible reference dextran was determined to be 1%, suggesting that the blood brain barrier tends to restrict peptide penetration.