Update of P2X receptor properties and their pharmacology:IUPHAR Review 30

Illes, Peter, Müller, Christa E., Jacobson, Kenneth A., Grutter, Thomas, Nicke, Annette, Fountain, Samuel J, Kennedy, Charles, Schmalzing, Günther, Jarvis, Michael F., Stojilkovic, Stanko S., King, Brian F. and Di Virgilio, Francesco (2020) Update of P2X receptor properties and their pharmacology:IUPHAR Review 30. British Journal of Pharmacology. ISSN 0007-1188

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Abstract

The known seven mammalian receptor (R) subunits (P2X1-7) form cationic channels gated by ATP. Three subunits compose a receptor-channel. Each subunit is a polypeptide consisting of two transmembrane regions (TM1, TM2), intracellular N- and C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D-structure and gating cycle of P2XRs. The agonist binding pocket is located at the intersection of two neighboring subunits. In addition to the mammalian P2XRs their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2XR subtypes are not available, but medicinal chemistry supplied a range of subtype selective antagonists, as well as positive and negative allosteric modulators. Knockout mice and selective antagonists helped to identify pathological functions due to defective P2XRs, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).

Item Type: Article
Additional Information: This article is protected by copyright. All rights reserved.
Faculty \ School: Faculty of Science
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 03 Nov 2020 11:49
Last Modified: 11 Nov 2020 01:15
URI: https://ueaeprints.uea.ac.uk/id/eprint/77518
DOI: 10.1111/bph.15299

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