On the blood-brain barrier to peptides: accumulation of labelled vasopressin, DesGlyNH2-vasopressin and oxytocin by brain regions.

After intracarotid injection of 125I-arginine vasopressin (AVP), 125I- or 3H-lysine vasopressin (LVP), 3H-DesGlyNH2-arginine vasopressin (DGAVP), and 125I- or 3H-oxytocin (OXT), the accumulation of radioactivity was determined in 13 to 18 brain regions and anterior pituitary in rats. Calculated extraction by tight capillary regions amounts to about 1-2% independently of the peptide doses injected (4 X 10(-4) to 5 X 10(-9) mol-1). This indicates a low but measurable extraction of labelled peptides which furthermore is nonsaturable. Among brain regions with tight capillaries, the extraction does not vary obviously. Blood-brain barrier (BBB)-free regions extract up to 30 fold more peptide than BBB-protected regions and the extraction varies considerably between individual regions. Within BBB-free regions, the peptides passed the leaky capillary endothelium, but there is no evidence for a penetration to deeper layers of the brain. It is concluded that endogenous blood-borne peptides cannot pass brain barriers in physiologically significant amounts. This does not exclude a possibility that passive transport of minute but effective amounts might occur if high pharmacological amounts of peptides are injected peripherally. But, as shown, none of the peptides studied possesses properties that favour its passage across the BBB.