Ligand specificity and ticlopidine effects distinguish three human platelet ADP receptors

• Published in: European journal of pharmacology 1998-06, Vol.351 (2), p.235-246
• Main Authors: Geiger, Jörg, Hönig-Liedl, Petra, Schanzenbächer, Peter, Walter, Ulrich
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenylyl Cyclase Inhibitors; ADP derivative; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Ca 2; Calcium - metabolism; G-protein; Humans; Ion Transport; Ligands; Medical sciences; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - pharmacology; Purinoceptor; Receptors, Purinergic P2 - metabolism; Signal Transduction - drug effects; Thienopyridine; Ticlopidine - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00305-7

Human platelets express adenosine 5′-diphosphate (ADP)-specific purinoceptors of the P 2X and P 2Y 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 Ca 2+-influx, desensitization of Ca 2+-influx, Ca 2+-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 P 2X receptor and an antagonist for the P 2Y receptors. The ADP-receptor pathway-antagonist ticlopidine inhibited ADP-evoked aggregation and adenylyl cyclase inhibition but did not affect platelet purinoceptors associated with Ca 2+-influx and Ca 2+-mobilization. These results indicate the presence of three distinct ADP-selective purinoceptors on human platelets.