Evidence map›Paper›PMID 16934758›Full record

ArticleBiochemical pharmacology2006

Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12 receptors.

Liaman K Mamedova, Zhan-Guo Gao, Kenneth A Jacobson

Abstract read
In one paragraph

Article in Biochemical pharmacology, 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
2.1field-weighted citation impact, top 15% 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, 46 citations in OpenAlex.

  1. Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  2. Purinergic P2YPurinergic signalling · 2025
    Article
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  7. Microglia P2YFrontiers in pharmacology · 2018
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Purinergic signaling in embryonic and stem cell development.Cellular and molecular life sciences : CMLS · 2011
    Review
  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 2 institutions in 1 country.

Liaman K MamedovaMolecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA.
Zhan-Guo Gao
Kenneth A Jacobson
National Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · US

Funding

PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDESZ01DK031116 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 1991 to 2008
$769k
Intramural NIH HHS Z01 DK031116
6 · The paper itself

Abstract

ADP is the endogenous agonist for both P2Y(1) and P2Y(12) receptors, which are important therapeutic targets. It was previously demonstrated that ADP and a synthetic agonist, 2-methylthioadenosine 5'-diphosphate (2MeSADP), can induce apoptosis by activating the human P2Y(1) receptor heterologously expressed in astrocytoma cells. However, it was not known whether the P2Y(12) receptor behaved similarly. We demonstrated here that, unlike with the G(q)-coupled P2Y(1) receptor, activation of the G(i)-coupled P2Y(12) receptor does not induce apoptosis. Furthermore, activation of the P2Y(12) receptor by either ADP or 2MeSADP significantly attenuates the tumor necrosis factor alpha (TNFalpha)-induced apoptosis in 1321N1 human astrocytoma cells. This protective effect was blocked by the P2Y(12) receptor antagonist 2-methylthioAMP and by inhibitors of phospholipase C (U73122) and protein kinase C (chelerythrin), but not by the P2Y(1) receptor antagonist MRS2179. Toward a greater mechanistic understanding, we showed that hP2Y(12) receptor activation by 10nM 2MeSADP, activates Erk1/2, Akt, and JNK by phosphorylation. However, at a lower protective concentration of 100pM 2MeSADP, activation of the hP2Y(12) receptor involves only phosphorylated Erk1/2, but not Akt or JNK. This activation is hypothesized as the major mechanism for the protective effect induced by P2Y(12) receptor activation. Apyrase did not affect the ability of TNFalpha to induce apoptosis in hP2Y(12)-1321N1 cells, suggesting that the endogenous nucleotides are not involved. These results may have important implications for understanding the signaling cascades that follow activation of P2Y(1) and P2Y(12) receptors and their opposing effects on cell death pathways.

Indexed as

Purinergic P2 Receptor AgonistsAdenosineAdenosine DiphosphateAdenosine TriphosphateApoptosisApyraseAstrocytesCell Line, TumorCell SurvivalHumansIn Situ Nick-End LabelingProtein Serine-Threonine KinasesPurinergic P2 Receptor AntagonistsReceptors, Purinergic P2Receptors, Purinergic P2Y1Receptors, Purinergic P2Y122-methylthioadenosineAdenosineAdenosine DiphosphateAdenosine TriphosphateApyraseN(6)-methyl-2'-deoxyadenosine 3',5'-diphosphateP2RY12 protein, humanP2RY1 protein, humanProtein Serine-Threonine KinasesPurinergic P2 Receptor AgonistsPurinergic P2 Receptor AntagonistsReceptors, Purinergic P2Receptors, Purinergic P2Y1Receptors, Purinergic P2Y12ThionucleosidesTumor Necrosis Factor-alpha

Identifiers

PMID16934758
PMCPMC3150742
OpenAlexW1974430159

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.