Regional differences in peptide degradation by rat cerebral microvessels -A potential novel regulatory mechanism for communication between blood andbrain

The blood-brain barrier (BBB), composed of the microvessels of cerebral cap illary endothelial cells, regulates the passage of peptides into the brain in several ways, mainly by saturable transport or passive diffusion. Here w e describe an additional mechanism by which this regulatory function can oc cur. Cerebral microvessels were isolated from different regions of the brai n and incubated with the mu-opiate selective endomorphin-1 (Tyr-Pro-Trp-Phe -NH2) or the opiate-modulating Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), both tetrap eptides selectively tritiated at the Pro. Degradation was determined by HPL C. For both peptides, the metabolism by microvessels from the cerebral cort ex was much greater than that by microvessels from the hypothalamus or pons . For endomorphin-1, the least degradation was in the pons; for Tyr-MIF-1 t here was no difference in metabolism by microvessels from the pons or hypot halamus. The results show a novel mechanism at the BBB by which the BBB can selectively regulate the activity of different peptides in different regio ns of the brain. (C) 2001 Elsevier Science Inc. All rights reserved.