CoChat
Sign Up
Cited by 106Barrier Structure and Function StudiesAmino Acid Enzymes and MetabolismDrug Transport and Resistance Mechanisms

Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier

O'Kane, Robyn L., Hawkins, Richard A.·2003·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00193.2003
Open this paper in CoChat — free account

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…

Integrity signals

Registry

Crossref · 10.1152/ajpendo.00193.2003

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • All essential amino acids are transported into the brain across the blood-brain barrier via large neutral endothelial amino acid transporter 1 and 2 (LAT1/2), which transport bidirectionally large neutral amino acids such as tryptophan and tyrosine.

    “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]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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
DOI
10.1152/ajpendo.00193.2003
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review