Category: receptor_pharmacology
Purinergic signaling — Burnstock's framework, vindicated over 50+ years — comprises ATP-binding P2 receptors and adenosine-binding P1 receptors. This pathway covers P2 (ATP / ADP / UTP / UDP). The adenosine P1 family lives in [[adenosine_receptor_signaling]]. P2 splits into: (1) P2X (ionotropic — ATP-gated trimeric cation channels P2X1–7, fast ms-scale Ca²⁺/Na⁺ influx; P2X7 is the slow pore-forming subtype on macrophages → NLRP3 inflammasome trigger, cross-link [[pyroptosis_gasdermin]]); (2) P2Y (metabotropic GPCRs — P2Y1/2/4/6/11/12/13/14; Gq/Gi/Gs coupling varies). Sources of extracellular nucleotides: regulated release (synaptic vesicles, taste cells, autocrine via Cx43 / pannexin-1 hemichannels), passive release (cell stress, ischemia, injury — ATP as DAMP). Hydrolysis cascade: ATP → ADP → AMP → adenosine via CD39 (ENTPD1) + CD73 (NT5E) ecto-enzymes — links P2 to P1. Therapeutic landscape — best-developed at platelet P2Y12: clopidogrel + prasugrel (irreversible prodrugs requiring CYP activation), ticagrelor (reversible), cangrelor (IV reversible) are antiplatelet mainstays for ACS, PCI, stent thrombosis prevention. P2X7 antagonists trialed for inflammatory disease — programs largely abandoned. IV adenosine for SVT (transient AV block) and pharmacologic stress imaging via P1. Suramin = non-selective P2 antagonist (historical anti-trypanosomal). Cross-links: [[platelet_aggregation]] (P2Y12 antiplatelet pharmacology), [[adenosine_receptor_signaling]] (P1 sister family), [[pyroptosis_gasdermin]] (P2X7 → NLRP3).