Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier

Abstract

Regulation of neutral amino acid transport was studied using isolated plasma membrane vesicles derived from the bovine blood-brain barrier. Neutral amino acids cross the blood-brain barrier by facilitative transport system L1, which may allow both desirable and undesirable amino acids to enter the brain. The sodium-dependent amino acid systems A and B(o,+) are located exclusively on abluminal membranes, in a position to pump unwanted amino acids out. γ-Glutamyl transpeptidase, the first enzyme of the γ- glutamyl cycle, is an integral protein of the luminal membrane of the blood- brain barrier. We demonstrate that oxoproline, an intracellular product of the γ-glutamyl cycle, stimulates the sodium-dependent systems A and B(o,+) by 70 and 20%, respectively. Study of system A showed that 2 mM oxoproline increased the affinity for its specific substrate N-methylaminoisobutyrate by 50%. This relationship between the activity of the γ-glutamyl cycle and system A transport may provide a short term regulatory mechanism by which the entry of potentially deleterious amino acids (i.e. neurotransmitters or their precursors) may be retarded and their removal from brain accelerated.