Amino acid transport across each side of the blood-brain barrier.

Pyroglutamate stimulates Na+ -dependent glutamate transport across the blood-brain barrier.

Regulation of Na(+)-dependent glutamate transport was studied in isolated luminal and abluminal plasma membranes derived from the bovine blood-brain barrier. Abluminal membranes have Na(+)-dependent glutamate transporters while luminal membranes have facilitative transporters. This organization allows glutamate to be actively removed from brain. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle (GGC), is on the luminal membrane. Pyroglutamate (oxoproline), an intracellular product of GGC, stimulated Na(+)-dependent transport of glutamate by 46%, whereas facilitative glutamate uptake in luminal membranes was inhibited. This relationship between GGC and glutamate tra…

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

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,…

Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+.

Cationic amino acid (CAA) transport is brought about by two families of proteins that are found in various tissues: Cat (CAA transporter), referred to as system y+, and Bat [broad-scope amino acid (AA) transporter], which comprises systems b0,+, B0,+, and y+L. CAA traverse the blood-brain barrier (BBB), but experiments done in vivo have only been able to examine the BBB from the luminal (blood-facing) side. In the present study, plasma membranes isolated from bovine brain microvessels were used to identify and characterize the CAA transporter(s) on both sides of the BBB. From these studies, it was concluded that system y+was the only transporter present, with a prevalence of activity on the…

Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids

Brain capillary endothelial cells form the blood-brain barrier (BBB). They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins mediates amino acid (AA) homeostasis in the brain. The existence of two facilitative transporters for neutral amino acids (NAAs) on both membranes provides the brain access to essential AAs. Four Na(+)-dependent transporters of NAA exist in the abluminal membranes of the BBB. Together these systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and from…