P2RX3 (purinergic receptor P2X 3; HGNC:8534, NCBI Gene ID 5024) is a human locus mapped to chromosome band 11q12.1 that encodes P2X3 purinergic trimeric ligand-gated ion channel subunit (397 aa). P2RX3 acts in extracellular ATP purinergic mechanonociception & vagal cough reflex, together with P2X Purinergic Receptors, P2Y Purinergic Receptors, and Adenosine Triphosphate (Synaptic ATP). Encodes the ATP-gated P2X3 ion channel subunit mediating purinergic pain and cough reflexes.
Approved Symbol
P2RX3
Chromosomal Locus
11q12.1
Encoded Product
P2X3 purinergic trimeric ligand-gated ion channel subunit (397 aa)
Primary Pathway
Extracellular ATP purinergic mechanonociception & vagal cough reflex
Clinical / Therapeutic Role
Target of selective P2X3 antagonists (gefapixant, camlipixant) for refractory chronic cough
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 12-exon gene at 11q12.1 encoding a 397-amino-acid subunit with two transmembrane domains, intracellular N- and C-termini, and a large disulfide-rich extracellular ATP-binding ectodomain that assembles into P2X3 homotrimers or P2X2/3 heterotrimers.
Cellular & Tissue Expression Profile: Predominantly expressed in small-diameter non-peptidergic IB4-positive nociceptive neurons of dorsal root and trigeminal ganglia and in vagal C-fiber afferents innervating the respiratory epithelium and urinary bladder urothelium.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Binds micromolar extracellular adenosine triphosphate (ATP) released from mechanically distended, inflamed, or damaged epithelial cells, gating rapid Na+ and Ca2+ influx that initiates action potentials in visceral pain and airway cough pathways.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Up-regulation of P2RX3 expression and membrane trafficking in dorsal root and nodose ganglia drives visceral hypersensitivity in interstitial cystitis, endometriosis, and chronic neuropathic pain models.
Therapeutic & Clinical Pharmacology: First-in-class allosteric P2X3 antagonists such as gefapixant and highly P2X3-selective second-generation blockers (camlipixant, eliapixant) suppress vagal C-fiber hyperexcitability in refractory chronic cough while minimizing P2X2/3 taste-bud dysgeusia.