No evidence has been reported to date which indicates that peptides such as insulin, the enkephalins, or TRH traverse the BBB by specific transport systems. Therefore, the use of latentiated (lipid-soluble) derivatives of peptides provides the most practical approach to circumvent the restricted permeability of the BBB to peptides. In contrast to the BBB, the blood-CSF barrier appears to selectively transport certain peptides (e.g., insulin) or plasma proteins (e.g., prealbumin) from blood into CSF. However, since the surface area of the BBB is 5,000-fold greater than the surface area of the blood-CSF barrier, it is unlikely that transport through the blood-CSF barrier permits rapid distribution of circulating peptides into brain interstitial space. 2. The presence of BBB peptide receptors such as those which have recently been demonstrated for insulin (ref. 32 and fig. 2), provides a mechanism by which neuropeptides may transmit signals to the brain side of the BBB via binding and activate receptors on the blood side of the BBB. In this way, circulating neuropeptides may potentially rapidly influence brain activity without traversing the BBB or entering brain interstitial or synaptic spaces.
