Permeability of the blood-brain barrier to neuropeptides: the case for penetration.

Evidence that peptides can cross the blood-brain barrier (BBB) is reviewed. Penetration is suggested by the observations that blood levels correlate with cerebrospinal fluid levels for many peptides and that peripheral administration of peptides results in effects on the CNS. Passage is confirmed by experiments involving administration of a peptide (immunoactive or radioactive) in one compartment and identification of its appearance in the other, supported by such methods as selective labeling, cross-reactivity with highly specific antibodies, and chromatography. The degree of passage varies among peptides and their analogs. The major route of passage is probably by a non-competitive, non-saturable mechanism, wih the physicochemical characteristics of the peptide (e.g. lipophilicity, charge, molecular weight, and protein binding) determining the degree of passage. A competitive transport mechanism also exists for some peptides. Penetration of the BBB via large pores or by pinocytosis does not appear to be of major importance for peptides. Permeability of the BBB to peptides, but not to the larger iodinated albumin, is affected by intraperitoneal administration of aluminum, apparently by an increase in the permeability of the membrane to lipophilic materials.