Summary: The brain is both the source and the recipient of peptide signals, The question is: Do endogenous, blood-borne peptide molecules influence brain function?Brain regions with the tight capillaries of the blood-brain barrier (BBB) extract low but measurable amounts of la beled peptide molecules from an intracarotid bolus injec tion, In the rat, the extraction fractions of f3-casomor phin-5, DesGlyNH2-arginine-vasopressin, arginine-vaso pressin, lysine-vasopressin, oxytocin, gonadoliberin, substance P, and f3-endorphin, studied in this laboratory, range from 0.5% (substance P) to 2.4% (arginine-vaso pressin). Extraction varies little among the 15 examined brain regions. As shown for arginine-vasopressin, the ex tracted peptides may be bound in part to specific binding sites located on the luminal membrane of the tight en dothelial cells. Tr ansport of peptide molecules across the BBB cannot be ruled out, but it is unlikely that endoge nous peptides pass the BBB in physiologically significant amounts. In contrast, in brain regions with leaky capil- BRAIN AND PEPTIDESNeurons process information. The process in cludes the release of chemical signals such as ace tylcholine, catecholamines, indolamines, amino acids, and peptides [for review, see Ganong (1982)]. There is evidence that numerous neuronal cell pop ulations produce and release peptides [for review, see Swaab (1982)J. Certain peptides including va sopressin (VP) and oxytocin (OT) trigger events in the brain itself as well as in the periphery of the body (Sterba et aI., 1981). Thus, the neuropeptides may serve in at least two lines of communication (Ermisch, 1980). First, they may trigger events within the brain when released into the synaptic cleft, or second, they may trigger events within the 350laries, e.g., selected circumventricular organs including the pineal gland, neurohypophysis, and choroid plexus, the peptide fraction extracted approaches that of water.Within the circumventricular organs, the peptide mole cules actually reach the cellular elements of the tissue.However, no studies definitively show that pep tides reach neurons in the deeper layers of the brain. On the other hand, blood-borne peptides influence the BBB per meability by altering the transport of essential sub stances. The effect may be mediated by specific peptide binding sites located at the luminal membrane of the en dothelium. It is possible that the effect of peptides on the BBB is necessary for proper brain function. There is some evidence that peptides, released centrally into the synaptic clefts as well as peripherally into the blood stream, support complex brain performances by both of these pathways.

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After intracarotid injection of [3H]beta-casomorphin-5 (beta CM5) in rats, the accumulation of radioactivity was determined in 18 brain regions and the anterior pituitary. The relative accumulation in all regions significantly exceeded that of [3H]inulin by a factor of 2.5, indicating a low but measurable brain uptake of the peptide. In blood-brain barrier-free areas, the accumulation of radioactivity was 15-fold higher than in blood-brain barrier-protected areas. The relative accumulation was not dependent on the total beta CM5 concentration in the range of 0.3-1.1 microM, and was not depressed by 400 microM L-tyrosine. We conclude that beta CM5, like other peptides, is accumulated in the blood-brain barrier-free areas to a relatively high but differing degree, whereas in the areas with a tight endothelium the accumulation is relatively low and nearly uniform. A binding to endothelial cells may contribute to the low accumulation of beta CM5, especially in blood-brain barrier-protected areas.

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