ADP-DEPENDENCE OF PLATELET ACTIVATION-INDUCED BY A THROMBIN RECEPTOR AGONIST

The synthetic peptide SFLLRNPNDKYEPF (Thrombin Receptor Agonist: TRA) has recently been shown to mimick the new amino-terminus created by cl eavage of the thrombin receptor on platelets and therefore to act as a receptor agonist. In the present work, this peptide proved a potent a ggregating agent for human platelets with an ED50 of 3 muM. The ADP re moving enzyme system creatine phosphate/creatine phosphokinase (CP/CPK ) and the ADP receptor antagonist ATPalphaS strongly inhibited platele t aggregation in response to low doses of TRA, indicating that TRA-ind uced platelet aggregation, like thrombin-induced aggregation is an ADP mediated event. CP/CPK had however no effect on aggregation in respon se to the agonist peptide at higher concentrations. Similar results we re obtained with regard to the influence of TRA and thrombin on platel et adenylyl cyclase activity, while both agents induced nucleotide rel ease from platelets in a dose-dependent manner. These results confirm that the aggregating effect of alpha-thrombin on human platelets is cl osely linked to its esterolytic activity at the receptor level and sho w that this aggregation is an ADP mediated event.