P2X purinoceptor (P2XR) (P2XR)

P2X purinoceptors are a family of seven ligand-gated ion channels (P2X1–P2X7) that are activated by extracellular adenosine triphosphate (ATP) [1][2]. These receptors are trimeric assemblies that, upon ATP binding, facilitate the rapid influx of cations such as sodium, potassium, and calcium, leading to membrane depolarization and the activation of various intracellular signaling pathways [3][4]. They are widely distributed throughout the body, playing essential roles in synaptic transmission, smooth muscle contraction, and the regulation of immune responses [1][4]. In pathological states, P2X receptors are heavily involved in the mediation of chronic pain, inflammatory conditions, and respiratory disorders like refractory chronic cough [3][5]. For example, P2X3 receptors are critical for sensory signaling in the airways, while P2X7 receptors are key drivers of the NLRP3 inflammasome and subsequent release of pro-inflammatory cytokines like IL-1β [1][6]. Consequently, P2X receptors have become significant therapeutic targets, with several subtype-specific antagonists, such as Gefapixant for chronic cough, being developed or approved to modulate these pathways [5][7]. However, drug development faces challenges such as achieving high selectivity to avoid side effects like taste disturbances (dysgeusia) caused by off-target inhibition of P2X2/3 heteromers [7].

Other names

ATP-gated ion channelPurinergic P2X receptorP2X receptor familyIonotropic purinoceptor

Antagonism of ATP-gated ion channels