P2X3 Receptor

P2X3 receptor (P2X purinoceptor 3) is an ATP-gated, trimeric cation channel predominantly expressed in sensory neurons, where it mediates extracellular ATP signaling and contributes to primary sensory transduction and nociceptive processing^[1][2][3]. Mechanistically, tissue injury, inflammation, or cellular stress can increase extracellular ATP levels, leading to activation of P2X3-containing receptors and amplification of sensory signaling pathways involved in pain and neurogenic responses^[2][4]. A distinctive feature of P2X3 is its rapid desensitization and slow recovery kinetics, properties that strongly influence the temporal pattern of sensory neuron excitation and ATP-dependent signal transmission^[5]. In disease-related contexts, P2X3-containing receptors have been implicated in chronic pain, bladder sensory dysfunction, and chronic cough, where excessive ATP-driven activation of sensory afferents contributes to pathological hypersensitivity^[2][4][6]. Compared with related P2X receptor isoforms, P2X3 can form both homomeric P2X3 channels and heteromeric P2X2/3 channels; these receptor assemblies play distinct roles in sensory neurons and are major mediators of ATP-evoked sensory responses^[3][7][8]. For experimental applications, selective P2X3 antagonists have become important pharmacological tools for dissecting purinergic signaling pathways, and the antagonist gefapixant has demonstrated clinical efficacy in refractory or unexplained chronic cough, supporting the translational relevance of P2X3-targeted modulation^[4][6].