Receptor-Mediated Peptide Transport through the Blood-Brain Barrier*

Abstract

THERE are at least two incentives for investigating the mechanisms of transport of peptides through the brain capillary wall, i.e. the blood-brain barrier (BBB). First, it is important to understand how circulating peptides, such as insulin, insulin-like growth factors (IGFs), transferrin, angiotensinogen, PTH, or others affect the brain, and these effects must necessarily involve the interface between blood and brain. Second, the vast promise of peptides as neuropharmaceuticals has not been realized, and this is due, in large part, to the fact that virtually all of the potential peptide pharmaceuticals are water soluble and, thus, are substantially excluded from entry into brain by the BBB. However, a major purpose of this review is to emphasize that knowledge of the physiological mechanisms that mediate the transport of peptides through the BBB may lead to the development of new strategies for delivery of peptide pharmaceuticals to brain.