Trial reportBlood2007
Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A.
Trial report in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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.
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.
Who cites it
40 citing papers in PubMed, 82 citations in OpenAlex.
- Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.Stroke · 2021Trial
- Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Trial
- The Effects of Milrinone Systemic Administration on Cerebral Perfusion as Measured with Computed Tomography in Aneurysmal Subarachnoid Hemorrhage Patients.Neurocritical care · 2026Observational
- Pan-cancer ex vivo target evaluation of phosphodiesterase 3 A (PDE3A).Journal of molecular medicine (Berlin, Germany) · 2026Article
- Differential regulation of cyclic adenosine monophosphate by phosphodiesterase 3A discriminates thrombin-induced protease activated receptor 1- and 4-dependent platelet activation.Journal of thrombosis and haemostasis : JTH · 2026Article
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- A disrupted adenosinergic axis facilitates platelet activation in APS: exploring a novel therapeutic target.Blood advances · 2025Article
- Unbiased high-throughput screening of drug-repurposing libraries identifies small-molecule inhibitors of clot retraction.Blood advances · 2025Article
- Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.Leukemia · 2025Article
- Article
- GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex.Biomolecules · 2023Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics.Journal of personalized medicine · 2021Article
- Prevention of platelet aggregation and arterial thrombosis using a modified Shenzhu Guanxin Formula.The Journal of international medical research · 2020Article
- Mechanistic insights into cancer cell killing through interaction of phosphodiesterase 3A and schlafen family member 12.The Journal of biological chemistry · 2020Article
- Linagliptin Regulates the Mitochondrial Respiratory Reserve to Alter Platelet Activation and Arterial Thrombosis.Frontiers in pharmacology · 2020Article
- Gradient-dependent inhibition of stimulatory signaling from platelet G protein-coupled receptors.Haematologica · 2019Article
- PDE3A inhibitor anagrelide activates death signaling pathway genes and synergizes with cell death-inducing cytokines to selectively inhibit cancer cell growth.American journal of cancer research · 2019Article
- Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.Nature genetics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Thrombin-induced cyclic AMP (cAMP) reduction potentates several steps in platelet activation, including Ca(++) mobilization, cytoskeletal reorganization, and fibrinogen receptor conformation. We now reinvestigate the signaling pathways by which intracellular cAMP content is controlled after platelet activation by thrombin. When washed human platelets were stimulated with thrombin, cAMP-dependent phosphodiesterase (PDE3A) activity was significantly increased. A nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX), and the PDE3 selective inhibitors milrinone and cilostazol each suppressed thrombin-induced cAMP-dependent PDE responses, but not 2 different PDE2 inhibitors. Selective inhibition of PDE3A resulted in reversal of thrombin-induced cAMP reduction, indicating that thrombin activated PDE3A. In synergy with inhibition of adenylate cyclase by thrombin, activated PDE3A accelerates cAMP hydrolysis and maximally reduces the cAMP content. Thrombin-induced PDE3A activation was diminished concomitantly with dephosphorylation of PDE3A by protein phosphatase 1 (PP1). An Akt inhibitor blocked PDE3A activation and constrained thrombin-induced cAMP reduction. A P2Y(12) inhibitor also reduced thrombin-induced cAMP reduction. The combination of both reversed cAMP decrease by thrombin. Thrombin-mediated phosphorylated PDE3A was isolated by liquid chromatography, detected by a monoclonal antibody against Akt-phosphorylated substrate, and verified by immunoprecipitation study. The predominant isoform phosphorylated by Akt was the 136-kDa species. We suggest that activation/phosphorylation of PDE3A via Akt signaling pathway participates in regulating cAMP during thrombin activation of platelets.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.