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Volume 271, Number 32, Issue of August 9, 1996 pp. 19129-19133
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Role of Oxoproline in the Regulation of Neutral Amino Acid Transport across the Blood-Brain Barrier

(Received for publication, December 19, 1995, and in revised form, May 7, 1996)

Wha-Joon Lee , Richard A. Hawkins , Darryl R. Peterson and Juan R. Viña ^¶

From the  Department of Physiology and Biophysics, Finch University of Health Science/The Chicago Medical School, North Chicago, Illinois 60064-3095, and the ^¶ Departamento de Bioquímica y Biología, Molecular Facultades de Medicina y Farmacia, Universitat de Valencia, Valencia 46010, Spain

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. -Glutamyl transpeptidase, the first enzyme of the -glutamyl cycle, is an integral protein of the luminal membrane of the blood-brain barrier. We demonstrate that oxoproline, an intracellular product of the -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 -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.

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