ArticleACS pharmacology & translational science2025
Species Differences of P2X4 Receptor Modulators.
Article in ACS pharmacology & translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
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Who cites it
5 citing papers in PubMed.
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- A brain-penetrant P2X7R antagonist mitigates Alzheimer's disease pathology.bioRxiv : the preprint server for biology · 2026Article
- Discovery of an allosteric binding site for anthraquinones at the human P2X4 receptor.Nature communications · 2025Article
- Towards P2X4 Positron Emission Tomography Tracing.Journal of medicinal chemistry · 2025Review
- The Construction Strategy of Curcumin Nanomedicine Delivery System and Its Application in the Treatment of Ulcerative Colitis.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The P2X4 receptor is an ATP-gated ion channel that was proposed as a novel drug target for neuropathic pain, neurodegenerative diseases, epilepsy, and cancer. Animal models are indispensable for elucidating the role of receptors in health and disease and for drug development. Here, we present a systematic analysis and comparison of P2X4 receptors of nine different species that are relevant for basic and applied research, human, monkey, dog, guinea pig, pig, rabbit, rat, mouse, and zebrafish. 1321N1 astrocytoma cell lines stably expressing the respective receptor were generated by retroviral transfection. Calcium influx assays were performed to assess the effects of structurally diverse P2X4 receptor agonists and antagonists with the aim of exploring species differences. Most agonists showed significantly reduced potency in mice, rats, and zebrafish in comparison to the human P2X4 receptor. The physiological agonist ATP was more potent at monkey, rabbit, guinea pig, and pig P2X4 receptors (0.0285-0.0594 μM) than at the human ortholog (0.269 μM) and least potent at the zebrafish receptor (3.27 mM). 2-MeS-ATP exhibited similar potency (0.290-4.50 μM) in all investigated P2X4 receptor species except zebrafish and is therefore a suitable tool compound for studying P2X4 receptors across species. The allosteric P2X4 receptor antagonists BX430 and 5-BDBD displayed notable species differences, while the indole derivative PSB-OR-2020 blocked all investigated mammalian species with high potency (0.696-6.32 nM), exhibiting only minor species differences. These data will be valuable to support future in vitro and, in particular, in vivo studies.
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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.