PEPTIDE BLOOD-BRAIN-BARRIER INTERACTIONS - KINETICS AND DYNAMICS

Via the circumventricular organs (CVOs) the brain is accessible to peripheral peptidic signals since peptidic receptors, localized on neurons in this area, are capable of recognizing the blood-borne ligands. As far as the blood-brain barrier (BBB)-protected regions are concerned, uptake studies with 14 different peptide entities reveal that the fraction of peptides extracted from the blood can be divided into three subfractions: molecules specifically bound at the BBB, molecules non-specifically bound at the BBB, and peptide molecules that have crossed the BBB. Paying special attention to arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), a very small non-saturable subfraction exists representing the peptide molecules that have crossed the barrier. Taking into account its low endogenous concentration, the passage of a minute amount of peptides is without biological significance. Thus, from a phylogenetical point of view, a paracellular pathway to transfer peptides from the hemal milieu to the extracellular fluid compartment of the brain has not been developed. The existence of specific binding sites for certain peptides on the luminal membrane of the endothelial cells indicates that the BBB itself is a target for some peptides. The interaction of these receptors with AVP or ANP does not alter the simple diffusion of larger molecules across the BBB, however, the ligand-receptor interaction alters the transfer of substances essential for the brain. Thus AVP changes the transport of large neutral amino acids from blood to brain, whereas ANP alters the permeability-surface area product of water. The AVP effect on the capacity and affinity of the brain endothelial amino acid transporter seems to be only a special case of a more general principle: the transport of amino acids across the epithelium of the gut that forms the barrier between the chyme and the internal milieu is regulated by casomorphins. The significance of these results is discussed here with a view to developing strategies for supplying the brain with peptides.