ArticleBritish journal of pharmacology2011
Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Review
- Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.Frontiers in pharmacology · 2024Review
- Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.Cell & bioscience · 2023Review
- Agonists, Antagonists, and Modulators of P2X7 Receptors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors.Pharmaceutics · 2020Review
- P2X7 Receptor Antagonism as a Potential Therapy in Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2020Review
- The P2X7 Receptor: Central Hub of Brain Diseases.Frontiers in molecular neuroscience · 2020Review
- [European journal of nuclear medicine and molecular imaging · 2019Article
- P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Synthesis and in vitro characterization of a P2X7 radioligand [European journal of pharmacology · 2018Article
- The role of microglial P2X7: modulation of cell death and cytokine release.Journal of neuroinflammation · 2017Article
- An In Vitro Caseum Binding Assay that Predicts Drug Penetration in Tuberculosis Lesions.Journal of visualized experiments : JoVE · 2017Article
- Pharmacologic characterizations of a P2X7 receptor-specific radioligand, [11C]GSK1482160 for neuroinflammatory response.Nuclear medicine communications · 2017Article
- Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks.European journal of nuclear medicine and molecular imaging · 2017Review
- P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia.Frontiers in cellular neuroscience · 2017Article
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
- NAD(+) regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4(+) CD25(+) Foxp3(+) T cells independent.Scientific reports · 2016Article
- Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine.The journal of headache and pain · 2014Article
- Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567.British journal of pharmacology · 2013Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described. EXPERIMENTAL APPROACH: Autoradiography studies using the P2X7 antagonist radioligand [³H]-A-804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate. KEY
resultsP2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, k(on) and k(off) values of 0.0021·min⁻¹·nM⁻¹ and 0.0070·min⁻¹ were determined, and the K(d) derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of [³H]-A-804598 to rat cortex P2X7 receptors with K(i) values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration-dependent inhibition of the specific binding of [³H]-A-804598 to rat cortex. CONCLUSIONS AND IMPLICATIONS: The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme.
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