Chapter 203 - Ingestive Peptides and the Blood—Brain Barrier

Abstract

This chapter discusses the transport mechanism of ingestive peptides across the blood-brain barrier (BBB). The BBB is a major regulatory interface coordinating a humoral-based communication between the gastrointestinal (GI) tract and the central nervous system (CNS). Leptin, insulin, and ghrelin are important examples of substances involved in this communication. Saturable transport systems in the brain or blood directions exist for many of these substances (leptin, insulin, and ghrelin). Other peptides cross by nonsaturable transmembrane diffusion. Their interactions with the BBB illustrate several principles, including the importance of saturable and nonsaturable mechanisms of passage, the regulation of BBB transporters, and the occurrence of disease with dysregulation of passage across the BBB. Specifically, the accumulation of substances by the brain from the blood is a balance between influx and efflux rates. Influx rates and CNS accumulation are primarily determined by the presence or absence of saturable transporters, the physicochemical properties of the substance, which, in turn, determine the rate of nonsaturable transmembrane diffusion, the pharmacokinetic parameters (clearance from blood and volume of distribution), capillary sequestration, and binding in plasma. Efflux rates and CNS retention are determined by many factors including the presence or absence of saturable efflux transporters, cerebrospinal fluid (CSF) reabsorption, degradation with the CNS, and uptake and sequestration by CNS tissues. The saturable transport systems are themselves regulated by physiological parameters and can be affected in disease states.