Blood-brain barrier and feeding: Regulatory roles of saturable transport systems for ingestive peptides

The two main ways for peptides in the peripheral body to enter the brain are by either saturable transport or passive diffusion across the blood-brain barrier (BBB). Saturable transport systems have the advantage of being responsive to physiological and pathological stimuli. Since saturable systems can regulate peptide entry into the brain, they have the potential to play controlling roles in feeding behavior. For therapeutic applications, however, saturable systems have the disadvantage of functioning as a threshold to limit access of large amounts of peptides into the brain. This pharmacological problem presumably would not be encountered for peptides crossing the BBB by passive diffusion, a process dependent on physicochemical properties. Thus, the gatekeeper function of the BBB can be expanded to a primary governing role, especially for entry of ingestive peptides subject to their respective saturable transport systems.