ArticleBlood2015
Impaired platelet activation and cAMP homeostasis in MRP4-deficient mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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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.
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Who cites it
20 citing papers in PubMed, 57 citations in OpenAlex.
- Identifying transcription factors controlling the basal expression of human MRP4 highlights a substantial role for Sp1.FEBS open bio · 2026Article
- Structural basis of prostaglandin efflux by MRP4.Nature structural & molecular biology · 2024Article
- Thrombopoietin-independent generation of platelet-like particles from megakaryoblastic cells.Scientific reports · 2023Article
- Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.Haematologica · 2022Article
- Multidrug-resistant protein inhibitor and phosphodiesterase inhibitor potentiate the vasodilator effect induced by photobiomodulation in isolated aortic rings.Lasers in medical science · 2022Article
- MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation.Journal of thrombosis and thrombolysis · 2021Article
- Platelet δ-Storage Pool Disease: An Update.Journal of clinical medicine · 2020Review
- The Systems Biology of Drug Metabolizing Enzymes and Transporters: Relevance to Quantitative Systems Pharmacology.Clinical pharmacology and therapeutics · 2020Review
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- Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia.Haematologica · 2020Article
- MiR-21 role in aspirin-dependent PPARα and multidrug resistance protein 4 upregulation.Research and practice in thrombosis and haemostasis · 2018Article
- Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.JACC. Basic to translational science · 2018Article
- The life cycle of platelet granules.F1000Research · 2018Review
- Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling.Purinergic signalling · 2017Review
- ABC Transport Proteins in Cardiovascular Disease-A Brief Summary.Molecules (Basel, Switzerland) · 2017Review
- Article
- Review
- Multispecific Organic Cation Transporter 1 (OCT1) from Bos taurus Has High Affinity and Slow Binding Kinetics towards Prostaglandin E2.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecules that reduce the level of cyclic adenosine 5'-monophosphate (cAMP) in the platelet cytosol, such as adenosine 5'-diphosphate (ADP) secreted from dense granules, trigger platelet activation. Therefore, any change in the distribution and/or availability of cyclic nucleotides or ADP may interfere with platelet reactivity. In this study, we evaluated the role of multidrug resistance protein 4 (MRP4, or ABCC4), a nucleotide transporter, in platelet functions in vivo and in vitro by investigating MRP4-deficient mice. MRP4 deletion resulted in a slight increase in platelet count but had no impact on platelet ultrastructure. In MRP4-deficient mice, the arterial occlusion was delayed and the tail bleeding time was prolonged. In a model of platelet depletion and transfusion mimicking a platelet-specific knockout, mice injected with MRP4(-/-) platelets also showed a significant increase in blood loss compared with mice injected with wild-type platelets. Defective thrombus formation and platelet activation were confirmed in vitro by studying platelet adhesion to collagen in flow conditions, integrin αIIbβ3 activation, washed platelet secretion, and aggregation induced by low concentrations of proteinase-activated receptor 4-activating peptide, U46619, or ADP. We found no role of MRP4 in ADP dense-granule storage, but MRP4 redistributed cAMP from the cytosol to dense granules, as confirmed by increased vasodilator-stimulated phosphoprotein phosphorylation in MRP4-deficient platelets. These data suggest that MRP4 promotes platelet aggregation by modulating the cAMP-protein kinase A signaling pathway, suggesting that MRP4 might serve as a target for novel antiplatelet agents.
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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 Socratic graph.