Evidence map›Paper›PMID 16809361›Full record

ArticleThe Journal of physiology2006

Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP.

David Reigada, Wennan Lu, Claire H Mitchell

Open access · greenAbstract read
In one paragraph

Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-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

24 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise.Documenta ophthalmologica. Advances in ophthalmology · 2026
    Review
  2. Implication ofInternational journal of molecular sciences · 2021
    Article
  3. Article
  4. Review
  5. Thrombin induces CaMolecular vision · 2019
    Article
  6. Article
  7. Article
  8. Expression of anoctamins in retinal pigment epithelium (RPE).Pflugers Archiv : European journal of physiology · 2016
    Article
  9. Central GPR109A Activation Mediates Glutamate-Dependent Pressor Response in Conscious Rats.The Journal of pharmacology and experimental therapeutics · 2016
    Article
  10. Article
  11. Article
  12. Review
  13. Lysosomal alkalinization, lipid oxidation, and reduced phagosome clearance triggered by activation of the P2X7 receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    Article
  14. Article
  15. Article
  16. Probenecid, a gout remedy, inhibits pannexin 1 channels.American journal of physiology. Cell physiology · 2008
    Article
  17. Review
  18. Article
  19. Article
  20. 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

3 authors at 1 institution in 1 country.

David ReigadaDepartment of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Wennan Lu
Claire H Mitchell
University of Pennsylvania · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
NEI NIH HHS EY001583NEI NIH HHS EY013434NEI NIH HHS EY015537NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY015537
6 · The paper itself

Abstract

The photoreceptors lie between the inner retina and the retinal pigment epithelium (RPE). The release of glutamate by the phototoreceptors can signal changes in light levels to inner retinal neurons, but the role of glutamate in communicating with the RPE is unknown. Since RPE cells are known to release ATP, we asked whether glutamate could trigger ATP release from RPE cells and whether this altered cell signalling. Stimulation of the apical face of fresh bovine RPE eyecups with 100 mum NMDA increased ATP levels more than threefold, indicating that both receptors for NMDA and release of ATP occurred across the apical membrane of fresh RPE cells. NMDA increased ATP levels bathing cultured human ARPE-19 cells more than twofold, with NMDA receptor inhibitors MK-801 and d-AP5 preventing this release. Blocking the glycine site of the NMDA receptor with 5,7-dichlorokynurenic acid prevented ATP release from ARPE-19 cells. Release was also blocked by channel blocker NPPB and Ca(2+) chelator BAPTA, but not by cystic fibrosis transmembrane conductance regulator (CFTR) blocker glibenclamide or vesicular release inhibitor brefeldin A. Glutamate produced a dose-dependent release of ATP from ARPE-19 cells that was substantially inhibited by MK-801. NMDA triggered a rise in cell Ca(2+) that was blocked by MK-801, by the ATPase apyrase, by the P2Y(1) receptor antagonist MRS2179 and by depletion of intracellular Ca(2+) stores with thapsigargin. These results suggest that glutamate stimulates NMDA receptors on the apical membrane of RPE cells to release ATP. This secondary release can amplify the glutaminergic signal by increasing Ca(2+) inside RPE cells, and might activate Ca(2+)-dependent conductances. The interplay between glutaminergic and purinergic systems may thus be important for light-dependent interactions between photoreceptors and the RPE.

Indexed as

Adenosine TriphosphateAnimalsCalciumCarrier ProteinsCattleCell LineDizocilpine MaleateDose-Response Relationship, DrugExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsGlutamic AcidHumansNerve Tissue ProteinsN-MethylaspartatePigment Epithelium of EyeReceptors, N-Methyl-D-AspartateAdenosine TriphosphateCalciumCarrier ProteinsDizocilpine MaleateExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsGlutamic AcidGRIN1 protein, humanNerve Tissue ProteinsN-MethylaspartateReceptors, N-Methyl-D-Aspartate

Identifiers

PMID16809361
PMCPMC1995677
OpenAlexW2160241140

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.