Purinergic P2X receptor 3 (P2X3)

Purinergic P2X receptor 3 is an **ATP-gated non-selective cation channel** predominantly expressed in peripheral sensory neurons. It belongs to the family of ligand-gated ion channels known as **Purinergic receptors**, specifically the **P2X subfamily**, which open upon binding extracellular adenosine triphosphate (ATP). The primary physiological role of this receptor involves mediating fast synaptic transmission in nociceptive pathways—especially those involved in sensing tissue damage or inflammation. It plays a critical part in various processes including **pain perception**, regulation of urinary bladder contraction, modulation of cough reflexes, and potentially insulin secretion. Due to its restricted expression pattern and central role in pathological states such as chronic pain syndromes and refractory chronic cough, it has become an important therapeutic target. Several small-molecule antagonists have been developed that act either competitively at the orthosteric site or allosterically at newly identified regulatory domains on the protein structure. Clinical development has focused primarily on conditions where aberrant purinergic signaling via this pathway contributes significantly to disease symptoms.[1][4][5][6]

Other names

P2RX3P2X purinoceptor 3ATP-gated ion channel P2X3Purinergic receptor P2X 3

Antagonism/inhibition of ATP binding to the ligand-gated cation channel, preventing depolarization and downstream signaling in sensory neurons. Allosteric modulation at a druggable site distinct from the orthosteric ATP-binding site; negative allosteric modulators reduce receptor activation by ATP.