Purinoceptor-evoked calcium signalling in human platelets

ADP evokes a rise in platelet cytosolic Ca2+ concentration by stimulating Ca2+ entry and releasing Ca2+ from intracellular stores. Single cell studies indicate that the response consists of a series of spikes in cytosolic Ca2+. The release of stored Ca2+ is mediated by the generation of inositol 1,4,5-trisphosphate. Store depletion in turn leads to activation of a store-regulated Ca2+ entry pathway via a mechanism which appears to involve a protein tyrosine phosphorylation step. Preceding these events, ADP activates a receptor-operated non-selective cation channel, which mediates the entry of Ca2+ and Na+ with a latency of just a few milliseconds. Recent studies indicate that this channel is activated via a P-2X1 purinoceptor at which ATP and diadenosine tetraphosphate are agonists. This receptor is distinct from that leading to the release of stored Ca2+ and to store-regulated Ca2+ entry.