Na+-dependent neutral amino acid transporters A, ASC, and N of the blood-brain barrier: mechanisms for neutral amino acid removal

• Published in: American journal of physiology: endocrinology and metabolism Vol. 287; no. 4; pp. E622 - E629
• Main Authors: O'Kane, Robyn L, Vina, Juan R, Simpson, Ian, Hawkins, Richard A
• Format: Journal Article
• Language: English
• Published: United States 01.10.2004
• Subjects: Algorithms; Amino Acid Transport Systems, Neutral - metabolism; Amino Acids, Neutral - metabolism; Animals; Blood-Brain Barrier - physiology; Cattle; Extracellular Fluid - metabolism; In Vitro Techniques; Kinetics; Lithium - metabolism; Membrane Potentials - physiology; Membranes - metabolism; Nerve Tissue Proteins - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00187.2004

1 Department of Physiology and Biophysics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064-3095; 2 Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain; and 3 Department of Neural and Behavioral Sciences, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 Submitted 29 April 2004 ; accepted in final form 25 May 2004 Four Na + -dependent transporters of neutral amino acids (NAA) are known to exist in the abluminal membranes (brain side) of the blood-brain barrier (BBB). This article describes the kinetic characteristics of systems A, ASC, and N that, together with the recently described Na + -dependent system for large NAA (Na + -LNAA), provide a basis for understanding the functional organization of the BBB. The data demonstrate that system A is voltage dependent (3 positive charges accompany each molecule of substrate). Systems ASC and N are not voltage dependent. Each NAA is a putative substrate for at least one system, and several NAA are transported by as many as three. System A transports Pro, Ala, His, Asn, Ser, and Gln; system ASC transports Ser, Gly, Met, Val, Leu, Ile, Cys, and Thr; system N transports Gln, His, Ser, and Asn; Na + -LNAA transports Leu, Ile, Val, Trp, Tyr, Phe, Met, Ala, His, Thr, and Gly. Together, these four systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and thence to the circulation. The existence of facilitative transport for NAA (L1) on both membranes provides the brain access to essential NAA. The presence of Na + -dependent carriers on the abluminal membrane provides a mechanism by which NAA concentrations in the ECF of brain are maintained at 10% of those of the plasma. active transport; brain extracellular fluid; capillaries; endothelial cells; essential amino acids Address for reprint requests and other correspondence: R. A. Hawkins, Dept. of Physiology and Biophysics, The Chicago Medical School, Rosalind Franklin Univ. of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064-3095 (E-mail: Richard.Hawkins{at}rosalindfranklin.edu )