Evidence map›Paper›PMID 11758761›Full record

ArticlePharmaceutical research2001

Effect of probenecid on fluorescein transport in the central nervous system using in vitro and in vivo models.

H Sun, D W Miller, W F Elmquist

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  4. Review
  5. Factors Influencing Luciferase-Based Bioluminescent Imaging in Preclinical Models of Brain Tumor.Drug metabolism and disposition: the biological fate of chemicals · 2022
    Article
  6. Understanding the brain uptake and permeability of small molecules through the BBB: A technical overview.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Review
  7. Article
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  12. Review
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  14. Article
  15. P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2009
    Article
  16. Neuroinflammation facilitates LIF entry into brain: role of TNF.American journal of physiology. Cell physiology · 2008
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

H SunDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha 68198-6025, USA.
D W Miller
W F Elmquist
University of Nebraska Medical Center · US

Funding

MRP-MEDIATED DRUG TRANSPORT IN THE BBBR29CA075466 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ELMQUIST, WILLIAM F · 1998 to 2002
$307k
ALTERED PGP AND MRP TRANSPORTERS IN BLOOD BRAIN BARRIERR03AG017294 · NIA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MILLER, DONALD W · 1999 to 1999
–
NCI NIH HHS CA-75466NIA NIH HHS R03AG-17294
6 · The paper itself

Abstract

purposeThe purpose of this study was to characterize the function of multidrug resistance-associated proteins (MRPs) (or MRP-like organic anion transport systems) in the blood-brain harrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) using both an in vitro BBB model and an in vivo microdialysis model.

methodsIn vitro functional studies were performed using bovine brain microvessel endothelial cells (BBMEC). The accumulation of fluorescein, an anionic fluorescent dye, in BBMEC was determined with and without the presence of inhibitors of various efflux transport proteins. In vivo microdialysis simultaneously monitored fluorescein concentrations in cortical extracellular fluid and cerebrospinal fluid. The effect of probenecid on the in vivo distribution of fluorescein was studied using a balanced crossover design in the rat.

resultsIn vitro experiments showed that probenecid, indomethacin, LY-329146, and all MRP inhibitors significantly increased (two- to threefold) the accumulation of fluorescein in BBMEC, whereas LY-335979, a P-gp inhibitor, had no effect on the accumulation of fluorescein. Probenecid significantly increased fluorescein plasma concentration and the plasma free fraction in vivo. The distribution of fluorescein across the BBB and BCSFB was enhanced by 2.2- and 1.9-fold, respectively, when probenecid was coadministered, even after correction for increased fluorescein plasma concentrations and free fraction.

conclusionsThese results demonstrate that MRPs or MRP-like transport system(s) may play an important role in fluorescein distribution across both BBB and BCSFB. This study showed that microdialysis proved to be a powerful in vivo technique for the study of transport systems in the central nervous system, and in vitro/in vivo correlations are possible using these model systems.

Indexed as

AlgorithmsAnimalsATP-Binding Cassette, Sub-Family C ProteinsBlood-Brain BarrierCalibrationCapillariesCattleCell SeparationCentral Nervous SystemEndothelium, VascularFluoresceinFluorescent DyesMicrodialysisModels, BiologicalProbenecidRatsATP-Binding Cassette, Sub-Family C ProteinsFluoresceinFluorescent DyesProbenecidUricosuric Agents

Identifiers

PMID11758761
OpenAlexW1502518199

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.