P2RX1

P2X purinergic receptor 1, commonly referred to as P2X1, is a member of the P2X receptor family of ATP-gated ion channels. It is a ligand-gated cation channel that opens in response to extracellular adenosine triphosphate (ATP). The receptor is believed to assemble as a trimer, with each subunit contributing two transmembrane segments and a large extracellular domain that binds ATP. Upon activation, P2X1 permits the influx of Na+, K+, and Ca2+, producing depolarization and downstream signaling. The channel desensitizes with prolonged ATP exposure.

P2X1 is expressed in a variety of tissues, with particularly high expression in blood platelets and vascular smooth muscle, as well as in some smooth muscles of the reproductive and urinary tracts and in certain peripheral neurons. In platelets, P2X1 contributes to rapid ATP-evoked responses that support platelet aggregation and thrombus formation. In smooth muscle, P2X1 mediates fast contractions, such as those in the vas deferens and other reproductive tissues, and it can participate in broader vascular and autonomic responses.

Pharmacology of P2X1 centers on ATP as the endogenous agonist and on a range of antagonists that inhibit receptor activity. Classic antagonists include suramin and PPADS, which are relatively nonselective. Research has identified more selective modulators and pore blockers in experimental studies, highlighting ongoing interest in P2X1 as a potential therapeutic target for disorders involving thrombosis and rapid smooth muscle contraction. Genetic or pharmacological disruption of P2X1 function can impair platelet aggregation and rapid smooth muscle responses, and animal models suggest effects on systems such as male fertility due to reduced contraction of the vas deferens.

The P2RX1 gene encodes the human P2X1 receptor. As part of the broader P2X receptor family, P2X1 can form homomeric channels and interacts with cellular signaling pathways that regulate calcium signaling and membrane excitability in response to extracellular ATP.