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

Author:

O’Kane Robyn L.,Viña Juan R.,Simpson Ian,Zaragozá Rosa,Mokashi Ashwini,Hawkins Richard A.

Abstract

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 abluminal membrane. System y+was voltage dependent and had a Kmof 470 ± 106 μM (SE) for lysine, a Kiof 34 μM for arginine, and a Kiof 290 μM for ornithine. In the presence of Na+, system y+was inhibited by several essential neutral AAs. The Kivalues were 3–10 times the plasma concentrations, suggesting that system y+was not as important a point of access for these AAs as system L1. Several small nonessential AAs (serine, glutamine, alanine,and glycine) inhibited system y+with Kivalues similar to their plasma concentrations, suggesting that system y+may account for the permeability of the BBB to these AAs. System y+may be important in the provision of arginine for NO synthesis. Real-time PCR and Western blotting techniques established the presence of the three known nitric oxide synthases in cerebral endothelial cells: NOS-1 (neuronal), NOS-2 (inducible), and NOS-3 (endothelial). These results confirm that system y+is the only CAA transporter in the BBB and suggest that NO can be produced in brain endothelial cells.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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