Evidence map›Paper›PMID 19346255›Full record

ArticleThe Journal of biological chemistry2009

The P2Y12 antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels.

Subhashini Srinivasan, Fozia Mir, Jin-Sheng Huang, Fadi T Khasawneh, Stephen C-T Lam, Guy C Le Breton

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Design and Pharmacological Characterization of a Novel Antithrombotic P2YInternational journal of molecular sciences · 2025
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  16. Racial differences in resistance to P2Y12 receptor antagonists in type 2 diabetic subjects.The Journal of pharmacology and experimental therapeutics · 2014
    Article
  17. Article
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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 1 institution in 1 country.

Subhashini SrinivasanFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612.
Fozia MirFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612.
Jin-Sheng HuangFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612.
Fadi T KhasawnehFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612.
Stephen C-T LamFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612.
Guy C Le BretonFrom the Department of Pharmacology, University of Illinois, Chicago, Illinois 60612. Electronic address: gcl@uic.edu.
University of Illinois Chicago · US

Funding

NHLBI NIH HHS HL23540-25
6 · The paper itself

Abstract

ADP plays an integral role in the process of hemostasis by signaling through two platelet G-protein-coupled receptors, P2Y1 and P2Y12. The recent use of antagonists against these two receptors has contributed a substantial body of data characterizing the ADP signaling pathways in human platelets. Specifically, the results have indicated that although P2Y1 receptors are involved in the initiation of platelet aggregation, P2Y12 receptor activation appears to account for the bulk of the ADP-mediated effects. Based on this consideration, emphasis has been placed on the development of a new class of P2Y12 antagonists (separate from clopidogrel and ticlopidine) as an approach to the treatment of thromboembolic disorders. The present work examined the molecular mechanisms by which two of these widely used adenosine-based P2Y12 antagonists (2-methylthioadenosine 5'-monophosphate triethylammonium salt (2MeSAMP) and ARC69931MX), inhibit human platelet activation. It was found that both of these compounds raise platelet cAMP to levels that substantially inhibit platelet aggregation. Furthermore, the results demonstrated that this elevation of cAMP did not require Gi signaling or functional P2Y12 receptors but was mediated through activation of a separate G protein-coupled pathway, presumably involving Gs. However, additional experiments revealed that neither 2MeSAMP nor ARC69931MX (cangrelor) increased cAMP through activation of A2a, IP, DP, or EP2 receptors, which are known to couple to Gs. Collectively, these findings indicate that 2MeSAMP and ARC69931MX interact with an unidentified platelet G protein-coupled receptor that stimulates cAMP-mediated inhibition of platelet function. This inhibition is in addition to that derived from antagonism of P2Y12 receptors.

Indexed as

Purinergic P2 Receptor AntagonistsAdenosine DiphosphateAdenosine MonophosphateAdenosine TriphosphateBlood PlateletsCyclic AMPDose-Response Relationship, DrugGTP-Binding Protein alpha Subunits, Gi-GoGuanosine DiphosphateHumansIn Vitro TechniquesPlatelet AggregationReceptor, Adenosine A2AReceptor, PAR-1Receptors, EpoprostenolReceptors, Immunologic2-methylthio-ATPAdenosine DiphosphateAdenosine MonophosphateAdenosine TriphosphatecangrelorCyclic AMPGTP-Binding Protein alpha Subunits, Gi-Goguanosine 5'-O-(2-thiodiphosphate)Guanosine DiphosphateP2RY12 protein, humanprostaglandin D2 receptorPTGER2 protein, humanPTGIR protein, humanPurinergic P2 Receptor AntagonistsReceptor, Adenosine A2AReceptor, PAR-1Receptors, EpoprostenolReceptors, ImmunologicReceptors, ProstaglandinReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReceptors, Purinergic P2Y12Receptors, Thromboxane A2, Prostaglandin H2Thionucleotides

Identifiers

PMID19346255
PMCPMC2713557
OpenAlexW2030753117

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.