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Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+.
Am J Physiol Endocrinol Metab. 2006 Aug; 291(2):E412-9.AJ

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 Km of 470 +/- 106 microM (SE) for lysine, a Ki of 34 microM for arginine, and a Ki of 290 microM for ornithine. In the presence of Na+, system y+ was inhibited by several essential neutral AAs. The Ki values 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 Ki values 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.

Authors+Show Affiliations

Natural and Applied Science Department, LaGuardia Community College/City University of New York, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16569760

Citation

O'Kane, Robyn L., et al. "Cationic Amino Acid Transport Across the Blood-brain Barrier Is Mediated Exclusively By System Y+." American Journal of Physiology. Endocrinology and Metabolism, vol. 291, no. 2, 2006, pp. E412-9.
O'Kane RL, Viña JR, Simpson I, et al. Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. Am J Physiol Endocrinol Metab. 2006;291(2):E412-9.
O'Kane, R. L., Viña, J. R., Simpson, I., Zaragozá, R., Mokashi, A., & Hawkins, R. A. (2006). Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. American Journal of Physiology. Endocrinology and Metabolism, 291(2), E412-9.
O'Kane RL, et al. Cationic Amino Acid Transport Across the Blood-brain Barrier Is Mediated Exclusively By System Y+. Am J Physiol Endocrinol Metab. 2006;291(2):E412-9. PubMed PMID: 16569760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. AU - O'Kane,Robyn L, AU - Viña,Juan R, AU - Simpson,Ian, AU - Zaragozá,Rosa, AU - Mokashi,Ashwini, AU - Hawkins,Richard A, Y1 - 2006/03/28/ PY - 2006/3/30/pubmed PY - 2006/9/13/medline PY - 2006/3/30/entrez SP - E412 EP - 9 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 291 IS - 2 N2 - 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 Km of 470 +/- 106 microM (SE) for lysine, a Ki of 34 microM for arginine, and a Ki of 290 microM for ornithine. In the presence of Na+, system y+ was inhibited by several essential neutral AAs. The Ki values 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 Ki values 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/16569760/Cationic_amino_acid_transport_across_the_blood_brain_barrier_is_mediated_exclusively_by_system_y+_ DB - PRIME DP - Unbound Medicine ER -