Peptides crossing the blood-brain barrier: some unusual observations

An interactive blood-brain barrier (BBB) helps regulate the passage of pept ides from the periphery to the CNS and from the CNS to the periphery. Many peptides cross the BBB by simple diffusion, mainly explained by their lipop hilicity and other physicochemical properties. Other peptides cross by satu rable transport systems. The systems that transport peptides into or out of the CNS can be highly specific, transporting MIF-1 but not Tyr-MIF-l, PACA P38 but not PACAP27, IL-I but not IL-2, and leptin but nut the smaller inge stive peptides NPY, orexin A, orexin B, CART (55-102[Met(O)(67)]), MCH, or AgRP(83-132). Although the peptides EGF and TGF-alpha bind to the same rece ptor, only EGF enters by a rapid saturable transport system, suggesting tha t receptors and transporters can represent different proteins. Even the pol ypeptide NGF enters faster than its much smaller subunit beta-NGF. The satu rable transport of some compounds can be upregulated, like TNF-alpha in EAE (an animal model of multiple sclerosis) and after spinal cord injury, emph asizing the regulatory role of the BBB. As has been shown for CRH, saturabl e transport from brain to blood can exert effects in the periphery. Thus, t he BBB plays a dynamic role in the communication of peptides between the pe riphery and the CNS. (C) 1999 Elsevier Science B.V. All rights reserved.