Ligand specificity and ticlopidine effects distinguish three human platelet ADP receptors.

Human platelets express adenosine 5'-diphosphate (ADP)-specific purinoceptors of the P2X and P2Y receptor superfamily, but their structure, diversity, and precise pharmacological profile is not well understood. Here, functional assays with intact platelets and well-characterized nucleotide derivatives were performed in order to characterize the ligand specificity of these platelet-specific purinoceptors. For the signalling pathways investigated (aggregation, rapid Ca2+-influx, desensitization of Ca2+-influx, Ca2+-mobilization, inhibition of adenylyl cyclase), significant differences in ligand specificity were demonstrated. ADP activated all purinoceptors of human platelets, while adenosine 5'-triphosphate (ATP) was a weak agonist for the P2X receptor and an antagonist for the P2Y receptors. The ADP-receptor pathway-antagonist ticlopidine inhibited ADP-evoked aggregation and adenylyl cyclase inhibition but did not affect platelet purinoceptors associated with Ca2+-influx and Ca2+-mobilization. These results indicate the presence of three distinct ADP-selective purinoceptors on human platelets.