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Physiological Consequences of the Passage of Peptides Across the Blood-Brain Barrier

Peptides given peripherally have been shown to affect the central nervous system (CNS). Peptides are also capable of crossing the blood-brain barrier (BBB). It is unclear, however, whether such crossing underlies the ability of peptides to affect the CNS. We review specific examples in which a peptide must cross the BBB to produce its effect. The effect elicited by passage often duplicates the effect elicited at peripheral sites of action. Other examples, however, are reviewed in which peptides have opposite effects after central and peripheral administration. Such paradoxical effects suggest that passage of peptides may be involved in feedback or counter-regulatory loops.