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.