The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier
Abstract
Several Na+-dependent carriers of amino acids exist on the abluminal membrane of the blood-brain barrier (BBB). These Na+-dependent carriers are in a position to transfer amino acids from the extracellular fluid of brain to the endothelial cells and thence to the circulation. To date, carriers have been found that may remove nonessential, nitrogen-rich, or acidic (excitatory) amino acids, all of which may be detrimental to brain function. We describe here Na+-dependent transport of large neutral amino acids across the abluminal membrane of the BBB that cannot be ascribed to currently known systems. Fresh brains, from cows killed for food, were used. Microvessels were isolated, and contaminating fragments of basement membranes, astrocyte fragments, and pericytes were removed. Abluminal-enriched membrane fractions from these microvessels were prepared. Transport was Na+ dependent, voltage sensitive, and inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, a particular inhibitor of the facilitative large neutral amino acid transporter 1 (LAT1) system. The carrier has a high affinity for leucine (Km 21 +/- 7 microM) and is inhibited by other neutral amino acids, including glutamine, histidine, methionine, phenylalanine, serine, threonine, tryptophan, and tyrosine. Other established neutral amino acids may enter the brain by way of LAT1-type facilitative transport. The presence of a Na+-dependent carrier on the abluminal membrane capable of removing large neutral amino a…
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“All essential AA are transported into the brain across the BBB via large neutral endothelial AA transporter 1 and 2 (LAT1/2) that transport bidirectionally large neutral AA such as tryptophan and tyrosine (450), and the cationic AA transporter 1 and 3 (CAT1/3)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [450]
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Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Tryptophan metabolism in the central nervous system: medical implications
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van Spronsen, F. J., Blau, N., Harding, C. O., Burlina, A., Longo, N., & Bosch, A. M. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00267-0 · Cited by 506
Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids
Hawkins, R. A., O’Kane, R. L., Simpson, I. A., & Viña, J. R. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.1.218s · Cited by 453
Self-citation
Metadata
- Authors
- O'Kane, R. L., & Hawkins, R. A.
- Affiliations
- Department of Physiology and Biophysics, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60064
- Rosalind Franklin University of Medicine and Science (US)
- ORCID
- Hawkins, Richard A.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2003-12
- Volume
- 285
- Issue
- 6
- Pages
- E1167-E1173
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2141267676
- Cited by
- 105
- References
- 55
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 5 · 2013: 1 · 2012: 3
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS041405, NS-041405)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, Na+-dependent amino acid transport, large neutral amino acids, LAT1, amino acid transporters, leucine, essential amino acids, excitatory amino acids, endothelial cells
- MeSH terms
- Amino Acids, Essential, Animals, Biological Transport, Active, Blood-Brain Barrier, Capillary Permeability, Cattle, Cell Membrane, Cell Membrane Permeability, Cells, Cultured, Endothelium, Vascular, Sodium, Extracellular Fluid
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