LIGAND SPECIFICITY AND TICLOPIDINE EFFECTS DISTINGUISH 3 HUMAN PLATELET ADP RECEPTORS

Human platelets express adenosine 5'-diphosphate (ADP)-specific purino ceptors of the P-2X and P-2Y receptor superfamily, but their structure , diversity, and precise pharmacological profile is not well understoo d. Here, functional assays with intact platelets and well-characterize d nucleotide derivatives were performed in order to characterize the l igand specificity of these platelet-specific purinoceptors. For the si gnalling pathways investigated (aggregation, rapid Ca2+-influx, desens itization of Ca2+-influx, Ca2+-mobilization, inhibition of adenylyl cy clase), significant differences in ligand specificity were demonstrate d. ADP activated all purinoceptors of human platelets, while adenosine 5'-triphosphate (ATP) was a weak agonist for the P-2X receptor and an antagonist for the P-2Y receptors, The ADP-receptor pathway-antagonis t ticlopidine inhibited ADP-evoked aggregation and adenylyl cyclase in hibition 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. (C) 19 98 Elsevier Science B.V. All rights reserved.