P2Y12 Receptor Antagonism Module

The receptor term here is specific where the calcium-sensing module had to settle for a generic one. GO:0001621 G protein-coupled ADP receptor activity names exactly what P2RY12 does, so the trigger binds it rather than the generic GO:0004930, and the gene binding (hgnc:18124) is corroboration rather than the only thing carrying the receptor identity. That is a difference in ontology coverage between receptors, not a claim that this one is better understood. The transducer step is sourced rather than assumed, and the sourcing is uneven in a way worth stating. That P2Y12 signals through Gi in human platelets is quoted from a study of platelet P2Y12 pharmacology, but that sentence is the authors restating their own earlier work, so it is graded BACKGROUND. The step from Gi to adenylate cyclase and cyclic AMP is quoted from a different paper whose subject is three natural products rather than a licensed antagonist, and whose cells are transfected HEK293 lines; it is cited for the pathway it maps and graded INDIRECT, not for its headline. The node does carry one direct measurement of its own quantity: basal cyclic AMP rises in human platelets when the receptor is blocked by selatogrel. That agent is investigational, so no cited abstract here measures the rise under a licensed P2Y12 inhibitor, and the node asserts the loss of the inhibition rather than a figure for it. The trigger is written for the class and not for one drug. Its own evidence quotes a paper on selatogrel, an investigational antagonist, because that paper's result names ticagrelor and elinogrel in the same sentence; what that sentence establishes is stabilization of the inactive Gi/o heterotrimer in cells with recombinant P2Y12, and only selatogrel is shown by cocrystal to stabilize the inactive receptor itself, so the trigger node is not written as a receptor-conformation claim for the class; the treatment block binds clopidogrel and ticagrelor, which are the two agents conformers in this knowledge base actually use. The irreversible thienopyridines and the reversible agents are not distinguished as separate nodes, because no conformer here turns on that difference and no abstract cited establishes a distinct downstream chain for it. Bleeding is modelled as a consequence arm rather than an adverse-effect aside, for the same reason hypocalcaemia is in casr_positive_allosteric_modulation: it is the same mechanism read at the organism scale, since a platelet that cannot be activated by ADP also cannot seal an injury. The cited source is a surgical trial whose premise is that patients still on ticagrelor bleed severely, which is the clearest statement of the risk in the sources gathered here rather than a quantified population rate. Three conformers are wired, all at the trigger: CADASIL_Type_1, Carotid_Stenosis and Coronary_Artery_Disease. Six further entries name a P2Y12 antagonist and are not wired, and the reasons divide into three kinds. Peripheral_Artery_Disease binds the generic NCIT:C1327 Antiplatelet Agent, which covers aspirin as well, so wiring it would assert P2Y12 action for a cyclooxygenase inhibitor; that is the same defect as the generic Bronchodilator binding that blocked Chronic_Obstructive_Pulmonary_Disease from the beta2 module until it was split. Carotid_Artery_Occlusion names clopidogrel in its treatment prose but binds only acetylsalicylic acid, so the agent would have to be bound before the treatment could be routed. Grange_syndrome, Kawasaki_Disease and Renal_Artery_Obstruction bind no agent at all on the relevant treatment, and Secondary_Erythromelalgia names ticlopidine only as one of the platelet inhibitors that failed to relieve its pain, inside a quoted result, so it is not treated with the class at all. What the six have in common, and the reason none is wired, is that no treatment in any of them binds a P2Y12 antagonist as therapeutic_agent. A bundled treatment is not itself an obstacle: CADASIL_Type_1 and Carotid_Stenosis both pair the antagonist with aspirin, and Carotid_Stenosis adds atorvastatin, but all bind their components as separate agents, so each receptor can take its own link.