Cited by 146Barrier Structure and Function StudiesPorphyrin Metabolism and DisordersDrug Transport and Resistance Mechanisms

Transport of 5-aminolevulinic acid between blood and brain

Ennis, S.R, Novotny, A, Xiang, J, Shakui, P, Masada, T, Stummer, W, Smith, D.E, Keep, R.F·2003·Brain Research

Abstract

Little is known about the movement of 5-aminolevulinic acid (delta-aminolevulinic acid; ALA) between blood and brain. This is despite the fact that increases in brain ALA may be involved in generating the neuropsychiatric symptoms in porphyrias and that systemic administration of ALA is currently being used to delineate the borders of malignant gliomas. The current study examines the mechanisms involved in the movement of [(14)C]ALA across the blood-brain and blood-CSF barriers in the rat. In the adult rat, the influx rate constant (K(i)) for [(14)C]ALA movement into brain was low ( approximately 0.2 microl/g per min), was unaffected by increasing plasma concentrations of non-radioactive ALA or probenecid (an organic anion transport inhibitor) and, therefore, appears to be a diffusional process. The K(i) for [(14)C]ALA was 3-fold less than that for [(14)C]mannitol, a molecule of similar size. This difference appears to result from a lower lipid solubility rather than saturable [(14)C]ALA transport from brain to blood. The K(i) for [(14)C]ALA for uptake into the neonatal brain was 7-fold higher than in the adult. However, again, this was unaffected by increasing plasma ALA concentrations suggesting a diffusional process. In contrast, at the blood-CSF barrier, there was evidence of carrier-mediated [(14)C]ALA transport from blood to choroid plexus and blood to CSF. Both processes were inhibited by administration of non-radioactive ALA and probenecid. However, experiments in choroid plexus epithelial cell primary cultures indicated that transport in these cells was polarized with [(14)C]ALA uptake from the apical (CSF) side being about 7-fold greater than uptake from the basolateral (blood) side. In total, these results suggest that the brain is normally fairly well protected from changes in plasma ALA concentration by the very low blood-brain barrier permeability of this compound and by a saturable efflux mechanism present at the choroid plexus.

Integrity signals

Registry

Crossref · 10.1016/s0006-8993(02)03749-6

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

We couldn’t retrieve this paper’s full text, 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?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Ennis, S. R., Novotny, A., Xiang, J., Shakui, P., Masada, T., Stummer, W., Smith, D. E., & Keep, R. F.
Affiliations
  • University of Michigan (US)
  • Ludwig-Maximilians-Universität München (DE)
Corresponding author
Keep, R.F
Venue
Brain Research
Publisher
Elsevier BV
Published
2003-01
Volume
959
Issue
2
Pages
226-234
ISSN
0006-8993 (ISSN-L)
OpenAlex
W2063825033
Cited by
146
References
31
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 6
FWCI
2.58
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL018575)
  • National Institute of General Medical Sciences (R01GM035498)
  • National Institute of Neurological Disorders and Stroke (R01NS034709)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
5-aminolevulinic acid, blood-brain barrier permeability, blood-CSF barrier, choroid plexus, diffusion, probenecid, neonatal brain, porphyria, choroid plexus epithelial cells, lipid solubility
MeSH terms
Aminolevulinic Acid, Animals, Biological Transport, Blood-Brain Barrier, Cerebral Cortex, Kidney, Rats, Inbred F344, Rats, Sprague-Dawley, Rats

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