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Fortuny-Gomez, Anna and Fountain, Samuel J. 
ORCID: https://orcid.org/0000-0002-6028-0548
(2024)
Pharmacological differences between human and mouse P2X4 receptor explored using old and new tools.
Purinergic Signalling, 20 (6).
pp. 659-667.
ISSN 1573-9538
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Abstract
There is growing interest in the P2X4 receptor as a therapeutic target for several cardiovascular, inflammatory and neurological conditions. Key to exploring the physiological and pathophysiological roles of P2X4 is access to selective compounds to probe function in cells, tissues and animal models. There has been a recent growth in selective antagonists for P2X4, though agonist selectivity is less well studied. As there are some known pharmacological differences between P2X receptors from different species, it is important to understand these differences when designing a pharmacological strategy to probe P2X4 function in human tissue and mouse models. Here, we provide a systematic comparison of agonist and antagonist pharmacology in 1321N1 cells expressing either human or mouse P2X4 orthologues. We identify a rank order of agonist potency of ATP > 2-MeSATP > αβmeATP = BzATP > CTP = γ-[(propargyl)-imido]-ATP for human P2X4 and ATP > 2-MeSATP = CTP > ATPγS = γ-[(propargyl)-imido]-ATP = BzATP for mouse. Human P2X4 is not activated by ATPγS but can be activated by αβmeATP. We identify a rank order of antagonist potency of BAY-1797 = PSB-12062 = BX-430 > 5-BDBD > TNP-ATP = PPADS for human P2X4 and BAY-1797 > PSB-12062 = PPADS > TNP-ATP for mouse. Mouse P2X4 is not antagonised by 5-BDBD or BX-430. The study reveals key pharmacological differences between human and mouse P2X4, highlighting caution when selecting tools for comparative studies between human and mouse and ascribing cellular responses of some commonly used agonists to P2X4.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability statement: Data presented with the manuscript are available on request from the corresponding author. Funding Information: This work was funded by a Biotechnology & Biological Sciences Research Council. |
| Uncontrolled Keywords: | human,mouse,p2x4,pharmacology,species difference,molecular biology,cellular and molecular neuroscience,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 28 Nov 2024 01:37 |
| Last Modified: | 19 Dec 2024 01:13 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97805 |
| DOI: | 10.1007/s11302-024-10018-x |
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