Evidence map›Paper›PMID 21381023›Full record

ArticleJournal of cellular physiology2012

Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow.

Ang Li, Chi Ting Leung, Kim Peterson-Yantorno, W Daniel Stamer, Claire H Mitchell, Mortimer M Civan

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 55 citations in OpenAlex.

  1. Trial
  2. Article
  3. Lowering the Intraocular Pressure in Rats and Rabbits byMolecules (Basel, Switzerland) · 2022
    Article
  4. Review
  5. Adenosine A3 receptor activated in HAnnals of translational medicine · 2021
    Article
  6. Review
  7. Adenosine receptors as promising targets for the management of ocular diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021
    Review
  8. Neuroinflammation in Primary Open-Angle Glaucoma.Journal of clinical medicine · 2020
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Regulatory Roles of Anoctamin-6 in Human Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2017
    Article
  15. Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  16. Observational
  17. Ocular Purine Receptors as Drug Targets in the Eye.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2016
    Review
  18. Article
  19. Review
  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

6 authors at 2 institutions in 1 country.

Ang LiDepartment of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA.
Chi Ting Leung
Kim Peterson-Yantorno
W Daniel Stamer
Claire H Mitchell
Mortimer M Civan
University of Pennsylvania · USUniversity of Arizona · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI Qi N Cui · 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
Aqueous Humor Outflow Control and Intraocular PressureR01EY013624 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CIVAN, MORTIMER MORDECAI · 2001 to 2013
$5.6M
CADHERIN DYNAMICS AND GLAUCOMAR01EY017007 · NEI · UNIVERSITY OF ARIZONA · PI STAMER, W DANIEL · 2006 to 2010
$1.7M
NEI NIH HHS EY01583NEI NIH HHS EY13624NEI NIH HHS EY15537NEI NIH HHS EY17007NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY013624NEI NIH HHS R01 EY015537NEI NIH HHS R01 EY017007
6 · The paper itself

Abstract

Our guiding hypothesis is that ecto-enzymatic conversion of extracellular ATP to adenosine activates A(1) adenosine receptors, reducing resistance to aqueous humor outflow and intraocular pressure. The initial step in this purinergic regulation is ATP release from outflow-pathway cells by mechanisms unknown. We measured similar ATP release from human explant-derived primary trabecular meshwork (TM) cells (HTM) and a human TM cell line (TM5). Responses to 21 inhibitors indicated that pannexin-1 (PX1) and connexin (Cx) hemichannels and P2X(7) receptors (P2RX(7) ) were comparably important in modulating ATP release induced by hypotonic swelling, whereas vesicular release was insignificant. Consistent with prior studies of PX1 activity in certain other cells, ATP release was lowered by the reducing agent dithiothreitol. Overexpressing PX1 in HEK293T cells promoted, while partial knockdown (KD) in both HEK293T and TM5 cells inhibited hypotonicity-activated ATP release. Additionally, KD reduced the pharmacologically defined contribution of PX1 and enhanced those of Cx and P2RX(7) . ATP release was also triggered by raising intracellular Ca(2+) activity with ionomycin after a prolonged lag time and was unaffected by the PX1 blocker probenecid, but nearly abolished by P2RX(7) antagonists. We conclude that swelling-stimulated ATP release from human TM cells is physiologically mediated by PX1 and Cx hemichannels and P2X(7) receptors, but not by vesicular release. PX1 appears not to be stimulated by intracellular Ca(2+) in TM cells, but can be modulated by oxidation-reduction state. The P2RX(7) -dependent component of swelling-activated release may be mediated by PX1 hemichannels or reflect apoptotic magnification of ATP release, either through itself and/or hemichannels.

Indexed as

AdenosineAdenosine TriphosphateAqueous HumorBlotting, WesternConnexinsGlaucomaHEK293 CellsHumansIntraocular PressureLuminescent MeasurementsMicroscopy, ConfocalNerve Tissue ProteinsReal-Time Polymerase Chain ReactionReceptors, Purinergic P2X7Reverse Transcriptase Polymerase Chain ReactionTrabecular MeshworkAdenosineAdenosine TriphosphateConnexinsNerve Tissue ProteinsPANX1 protein, humanReceptors, Purinergic P2X7

Identifiers

PMID21381023
PMCPMC3117029
OpenAlexW2017170271

What OpenQuestion holds

Textmetadata
LicenceTDM
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.