Blood-Brain Barrier Permeability to Excitatory Amino Acids

Abstract

The blood-brain barrier is situated at the layer of endothelial cells of brain capillaries (Rapoport, 1976; Bradbury, 1979). These cells are connected together by tight junctions, which prevent significant paracellular diffusion, and they contain very few transfer vesicles. As a consequence of these characteristics, a blood-borne solute must successively pass through the two membranes (luminal and antiluminal) and the cytoplasm of the endothelial cells before reaching the brain extracellular space. Molecules pass through the membranes by passive diffusion as a function of the lipid solubility of their undissociated form and of the extent of their dissociation at physiological pH (only the undissociated form is able to traverse the membranes). Molecules like amino acids, which are dissociated at normal pH, are thus nearly excluded from blood-brain transport unless they are transported by a specific carrier mechanism. These specific carriers are not all symmetrically distributed on the two membranes. Carriers on the luminal membrane seem to function mainly as exchange systems, while some carriers on the antiluminal membrane can produce active transport (Goldstein and Betz, 1983). An additional regulation of the passage of solutes can be exerted by cytoplasmic enzymes which can catabolize metabolites which have entered the endothelial cytoplasm (Bertler et al., 1966).