The P2X3 subunit: a molecular target in pain therapeutics.
P2X receptors are hetero-oligomeric proteins that function as membrane ion channels and are gated by extracellular ATP. The P2X3 subunit is a constituent of the channels on a subset of sensory neurons involved in pain signaling, where ATP released by damaged and inflamed tissue can initiate action potentials. The tissue distribution of this subunit, along with experiments using antagonists, antisense oligonucleotides and gene knockouts, suggests that it may be a useful target for the development of pain therapeutics. This has been substantiated by the development by Abbott of a small molecule that selectively blocks P2X3 subunit-containing P2X receptors, and which is effective in a range of animal models of neuropathic and chronic inflammatory pain.
North
R Alan
RA
Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. R.A.North@sheffield.ac.uk
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010146:Pain / Q000188:drug therapy* / Q000235:genetics; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058477:Receptors, Purinergic P2X3
C546407:P2RX3 protein, human; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3