title: P2T purinoceptors: ADP receptors on platelets.
abstract: ADP acts on platelets via the P2T purinoceptor to cause aggregation, but the way in which it does so is not fully understood. Most aggregating agents act via G protein-coupled receptors to stimulate phospholipase C (PLC) and so mobilize Ca2+ via inositol trisphosphate, whereas ADP clearly causes the mobilization of Ca2+ from internal stores but is only a weak activator of PLC. ADP also inhibits adenylate cyclase and it has been suggested that this effect is mediated by a different receptor, although evidence from antagonist studies argues against this. Studies of Ca2+ influx have shown that ADP is unique in causing a rapid influx of Ca2+, and patch-clamp studies have confirmed the activation by ADP of non-selective cation channels. This would imply the existence of two ADP receptors on platelets, a receptor-operated channel responsible for the rapid Ca2+ influx and a G protein-coupled receptor possibly linked to both inhibition of adenylate cyclase and mobilization of Ca2+. In this review the structure-activity relationships for aggregation, inhibition of adenylate cyclase and increases in cytoplasmic Ca2+ are summarized, and the relationship between these effects discussed.
authors.affiliation: Receptors and Cellular Regulation Research Group, School of Biological Sciences, University of Surrey, Guildford, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Hourani
authors.forename: D A
authors.initials: DA
authors.lastname: Hall
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D008565:Membrane Proteins; C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate