Evidence map›Paper›PMID 25832806›Full record

ArticleJournal of neurochemistry2015

Identification of P-glycoprotein co-fractionating proteins and specific binding partners in rat brain microvessels.

Margaret E Tome, Charles P Schaefer, Leigh M Jacobs, Yifeng Zhang, Joseph M Herndon, Fabian O Matty, Thomas P Davis

Open access · greenAbstract read
In one paragraph

Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
    Article
  5. Review
  6. Review
  7. Article
  8. P-glycoprotein traffics from the nucleus to the plasma membrane in rat brain endothelium during inflammatory pain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016
    Article
  9. Article
  10. Review
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

7 authors at 1 institution in 1 country.

Margaret E TomeDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Charles P SchaeferDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Leigh M JacobsDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Yifeng ZhangDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Joseph M HerndonDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Fabian O MattyDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Thomas P DavisDepartment of Medical Pharmacology, University of Arizona, Tucson, Arizona, USA.
Banner - University Medical Center Tucson · US

Funding

BLOOD BRAIN BARRIER CHANGES INDUCED BY PAINR01NS042652 · NINDS · UNIVERSITY OF ARIZONA · PI DAVIS, THOMAS PAUL · 2002 to 2017
$7.6M
BLOOD TO CNS UPTAKE OF OPIOID PEPTIDE DRUGSR01DA011271 · NIDA · UNIVERSITY OF ARIZONA · PI DAVIS, THOMAS PAUL · 1997 to 2014
$4.4M
NIDA NIH HHS DA 011271NIDA NIH HHS R01 DA011271NINDS NIH HHS NS 042652NINDS NIH HHS R01 NS042652
6 · The paper itself

Abstract

Drug delivery to the brain for the treatment of pathologies with a CNS component is a significant clinical challenge. P-glycoprotein (PgP), a drug efflux pump in the endothelial cell membrane, is a major factor in preventing therapeutics from crossing the blood-brain barrier (BBB). Identifying PgP regulatory mechanisms is key to developing agents to modulate PgP activity. Previously, we found that PgP trafficking was altered concomitant with increased PgP activity and disassembly of high molecular weight PgP-containing complexes during acute peripheral inflammatory pain. These data suggest that PgP activity is post-translationally regulated at the BBB. The goal of the current study was to identify proteins that co-localize with PgP in rat brain microvessel endothelial cell membrane microdomains and use the data to suggest potential regulatory mechanisms. Using new density gradients of microvessel homogenates, we identified two unique pools (1,2) of PgP in membrane fractions. Caveolar constituents, caveolin1, cavin1, and cavin2, co-localized with PgP in these fractions indicating the two pools contained caveolae. A chaperone (Hsc71), protein disulfide isomerase and endosomal/lysosomal sorting proteins (Rab5, Rab11a) also co-fractionated with PgP in the gradients. These data suggest signaling pathways with a potential role in post-translational regulation of PgP activity at the BBB.

Indexed as

AnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Blood-Brain BarrierBrainCapillary PermeabilityCaveolaeFemaleHSC70 Heat-Shock ProteinsImmunoblottingImmunoprecipitationMiceMicrovesselsProtein Disulfide-IsomerasesProtein TransportProteomicsRatsATP Binding Cassette Transporter, Subfamily B, Member 1HSC70 Heat-Shock ProteinsProtein Disulfide-IsomerasesATP synthase β subunitblood-brain barriercaveolaeP-glycoproteinprotein disulfide isomeraseRab5

Identifiers

PMID25832806
PMCPMC4490986
OpenAlexW2051226625

What OpenQuestion holds

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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.