P2X receptors: Insights from the study of the domestic dog

Sluyter, Ronald, Sophocleous, Reece A. and Stokes, Leanne ORCID: https://orcid.org/0000-0003-4013-6781 (2023) P2X receptors: Insights from the study of the domestic dog. Neuropharmacology, 224. ISSN 0028-3908

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Abstract

Fifty years ago, the late Geoffrey Burnstock described the concept of purinergic nerves and transmission bringing into existence the broader concepts of purinergic signaling including P2X receptors. These receptors are trimeric ligand-gated cation channels activated by extracellular adenosine 5′-triphosphate (ATP). P2X receptors have important roles in health and disease and continue to gain interest as potential therapeutic targets in inflammatory, neurological, cardiovascular and many other disorders including cancer. Current understanding of P2X receptors has largely arisen from the study of these receptors in humans and rodents, but additional insights have been obtained from the study of P2X receptors in the domestic dog, Canis familiaris. This review article will briefly introduce purinergic signaling and P2X receptors, before detailing the pharmacological profiles of the two recombinant canine P2X receptors studied to date, P2X7 and P2X4. The article will then describe the current state of knowledge concerning the distribution and function of the P2X receptor family in dogs. The article will also discuss the characterization of single nucleotide polymorphisms in the canine P2RX7 gene, and contrast this variation to the canine P2RX4 gene, which is largely conserved between dogs. Finally, this article will outline published examples of the use of dogs to study the pharmacokinetics of P2X7 and P2X3 antagonists, and how they have contributed to the preclinical testing of antagonists to human P2X7, CE-224,535, and human P2X3, Gefapixant (AF-219, MK-7264) and Eliapixant (BAY, 1817080), with Gefapixant gaining recent approval for use in the treatment of refractory chronic cough in humans.

Item Type: Article
Additional Information: Funding Information: The authors acknowledge funding from the American Kennel Club Canine Health Foundation, Australian Companion Animal Health Foundation and Canine Research Foundation supporting their research of canine P2 receptors.
Uncontrolled Keywords: canine,companion animal,extracellular adenosine 5′-triphosphate,ligand-gated ion channel,purinergic receptor,purinergic signaling,cellular and molecular neuroscience,pharmacology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2800/2804
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 15 Dec 2022 04:08
Last Modified: 03 Jan 2023 10:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/90154
DOI: 10.1016/j.neuropharm.2022.109358

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