TY - JOUR
T1 - Update of P2X receptor properties and their pharmacology: IUPHAR Review 30
AU - Illes, Peter
AU - Müller, Christa E.
AU - Jacobson, Kenneth A.
AU - Grutter, Thomas
AU - Nicke, Annette
AU - Fountain, Samuel J.
AU - Kennedy, Charles
AU - Schmalzing, Günther
AU - Jarvis, Michael F.
AU - Stojilkovic, Stanko S.
AU - King, Brian F.
AU - Di Virgilio, Francesco
N1 - This article is protected by copyright. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - The known seven mammalian receptor 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 and TM2), intracellular N- and C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D structure and gating cycle of P2X receptors. The agonist-binding pocket is located at the intersection of two neighbouring subunits. In addition to the mammalian P2X receptors, their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2X receptor 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 P2X receptors, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).
AB - The known seven mammalian receptor 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 and TM2), intracellular N- and C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D structure and gating cycle of P2X receptors. The agonist-binding pocket is located at the intersection of two neighbouring subunits. In addition to the mammalian P2X receptors, their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2X receptor 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 P2X receptors, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).
KW - (patho)physiological functions
KW - P2X receptors
KW - agonists
KW - antagonists
KW - extracellular ATP
KW - knockout mice
KW - ligand-gated cationic channels
UR - http://www.scopus.com/inward/record.url?scp=85095996977&partnerID=8YFLogxK
U2 - 10.1111/bph.15299
DO - 10.1111/bph.15299
M3 - Review article
C2 - 33125712
VL - 178
SP - 489
EP - 514
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 3
ER -