Evidence map›Paper›PMID 26542462›Full record

ArticleMolecular pain2015

p38 MAPK mediates glial P2X7R-neuronal P2Y1R inhibitory control of P2X3R expression in dorsal root ganglion neurons.

Yong Chen, Guangwen Li, Li-Yen Mae Huang

Open access · goldAbstract read
In one paragraph

Article in Molecular pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.2field-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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  7. Novel Therapeutic Approaches for Alzheimer's Disease: An Updated Review.International journal of molecular sciences · 2021
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  14. c-Abl-p38Molecular pain
    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.

Yong ChenDepartment of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555-1069, USA. yonchen@utmb.edu.
Guangwen LiDepartment of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555-1069, USA. gali@utmb.edu.
Li-Yen Mae HuangDepartment of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555-1069, USA. lmhuang@utmb.edu.
The University of Texas Medical Branch at Galveston · US

Funding

NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPYR01DE017813 · NIDCR · UNIVERSITY OF TEXAS MED BR GALVESTON · PI HUANG, LI-YEN M · 2006 to 2017
$3.9M
TRIGEMINAL NEURONS--SUSTAINED RESPONSE TO OPOIDSR01NS030045 · NINDS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI HUANG, LI-YEN M · 1993 to 2014
$3.7M
NIDCR NIH HHS DE017813NIDCR NIH HHS R01 DE017813NINDS NIH HHS NS030045NINDS NIH HHS R01 NS030045
6 · The paper itself

Abstract

backgroundWe have previously shown that endogenously active purinergic P2X7 receptors (P2X7Rs) in satellite glial cells of dorsal root ganglia (DRGs) stimulate ATP release. The ATP activates P2Y1Rs located in the enwrapped neuronal somata, resulting in down-regulation of P2X3Rs. This P2X7R-P2Y1-P2X3R inhibitory control significantly reduces P2X3R-mediated nociceptive responses. The underlying mechanism by which the activation of P2Y1Rs inhibits the expression of P2X3Rs remains unexplored.

resultsExamining the effect of the activation of p38 mitogen-activated protein kinase on the expression of P2X3Rs in DRGs, we found that the p38 activator, anisomycin (Anis), reduced the expression of P2X3Rs. Blocking the activity of SGCs by the glial Krebs cycle inhibitor, fluorocitrate, did not change the effect of Anis. These results suggest that neuronal p38 plays a major role in the inhibition of P2X3R expression. Western blotting analyses showed that inhibiting P2Y1Rs by MRS2179 (MRS) or blocking P2X7Rs by either oxATP or A740003 reduced pp38 and increased P2X3R expression in DRGs. These results are further supported by the immunohistochemical study showing that P2X7R and P2Y1R antagonists reduce the percentage of pp38-positive neurons. These observations suggest that activation of P2X7Rs and P2Y1Rs promotes p38 activity to exert inhibitory control on P2X3R expression. Since activation of p38 by Anis in the presence of either A740003 or MRS could overcome the block of P2X7R-P2Y1R inhibitory control, p38 in DRG neurons is downstream of P2Y1Rs. In addition, inhibition of p38 by SB202190 was found to prevent the P2X7R and P2Y1R block of P2X3R expression and increase P2X3R-mediated nociceptive flinch behaviors.

conclusionsp38 in DRG neurons downstream of P2Y1R is necessary and sufficient for the P2X7R-P2Y1R inhibitory control of P2X3R expression.

Indexed as

Adenosine DiphosphateAnimalsDown-RegulationEnzyme ActivationGanglia, SpinalImidazolesMalep38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsPyridinesRatsRats, Sprague-DawleyReceptors, Purinergic P2X3Receptors, Purinergic P2X7Receptors, Purinergic P2Y14-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazoleAdenosine DiphosphateImidazolesN(6)-methyl-2'-deoxyadenosine 3',5'-diphosphatep38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsPyridinesReceptors, Purinergic P2X3Receptors, Purinergic P2X7Receptors, Purinergic P2Y1

Identifiers

PMID26542462
PMCPMC4635984
OpenAlexW2166598836

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.