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.
Geiger
J
J
Medizinische Universitätsklinik, Institut für Klinische Biochemie und Pathobiochemie, Würzburg, Germany.
Hönig-Liedl
P
P
Schanzenbächer
P
P
Walter
U
U
D000244:Adenosine Diphosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008024:Ligands; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013988:Ticlopidine / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D008024:Ligands; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D000244:Adenosine Diphosphate; D013988:Ticlopidine; D002118:Calcium