Passage of peptides across the blood-brain barrier: pathophysiological perspectives

Blood-borne peptides are capable of affecting the central nervous system (CNS) despite being separated from the CNS by the blood-brain barrier (BBB), a monolayer comprised of brain endothelial and ependymal cells. Blood-borne peptides can directly affect the CNS after they cross the BBB by nonsaturable and saturable transport mechanisms. The ability of peptides to cross the BBB to a meaningful degree suggests that the BBB may act as a modulatory pathway in the exchange of informational molecules between the brain and the peripheral circulation. The permeability of the BBB to peptides is a regulatory process affected by developmental, physiological, and pathological events. This regulation sets the stage for the relation between peptides and the BBB to be involved in pathophysiological events. For example, some of the classic actions of melanocortins on the CNS are explained by their abilities to cross the BBB, whereas aspects of feeding and alcohol-related behaviors are associated with the passage of other specific peptides across the BBB. The BBB should no longer be considered a static barrier but should be recognized as a regulatory interface controlling the exchange of informational molecules, such as peptides, between the blood and CNS.