ReviewComputational and structural biotechnology journal2015
P2X4 receptor-eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure.
Review in Computational and structural biotechnology journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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.
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.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- MRS2339, a cardiac P2X4 receptor nucleotide activator, improves systolic function in heart failure.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Novel P2X4 Receptor Antagonist MRS4719 Improves Ischemia/reperfusion Injury in Mice.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Caveolin and NOS in the Development of Muscular Dystrophy.International journal of molecular sciences · 2024Review
- The Muscarinic Acetylcholine MCells · 2023Article
- The Pleiotropic Role of Extracellular ATP in Myocardial Remodelling.Molecules (Basel, Switzerland) · 2023Review
- Structure-Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2Journal of medicinal chemistry · 2022Article
- Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States.American journal of biomedical science & research · 2022Article
- Purinergic Regulation of Endothelial Barrier Function.International journal of molecular sciences · 2021Review
- P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors?Frontiers in pharmacology · 2020Review
- Dopamine Receptor Blockade Attenuates Purinergic P2X4 Receptor-Mediated Prepulse Inhibition Deficits and Underlying Molecular Mechanisms.Frontiers in cellular neuroscience · 2019Article
- The Ionotropic P2X4 Receptor has Unique Properties in the Heart by Mediating the Negative Chronotropic Effect of ATP While Increasing the Ventricular Inotropy.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na(+)) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF.
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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 OpenQuestion graph.