Blood-Brain Barrier Restriction of Peptides and the Low Uptake of Enkephalins*

Abstract

Blood-brain barrier penetration of leucine-enkephalin, methionine-enkephalin and other peptide-like compounds was measured after intracarotid injection of 3 isotopes and was nonsaturable over the nanomolar range of concentrations tested. No significant differences in brain regional extraction of leucine enkephalin (or morphine or heroin) were observed. The brain extraction [E] of enkephalins was minimally low (E = 2-3%) and about the same of magnitude as other putative neurotransmitters. Brain extractions of other peptide-like compounds were similarly small: TRH [thyroliberin], E = 1%; glutathione, E = 0.5%; .beta.-alanyl histidine, E = 1% 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.