cAMP is not an important messenger for ADP-induced platelet aggregation

In rat platelets, basal cAMP level did not vary significantly during ADP-induced aggregation. In the same conditions, no variation in the cAMP content was observed in platelets from rats treated with clopidogrel, whereas ADP-induced aggregation was totally inhibited ADP decreased cAMP level in control prostacyclin- or forskolin-stimulated platelets whereas, in treated platelets, adenylyl cyclase down-regulation was strongly inhibited SQ 22536 (500 mu M), an inhibitor of adenylyl cyclase, strongly reduced the cAMP content of both control and treated platelets but did not reverse the anti-aggregating activity of clopidogrel, showing that inhibition of ADP-induced adenylyl cyclase down-regulation in treated platelets was not responsible for the anti-aggregating effect of clopidogrel. Similar results were obtained in rabbit platelets. These results therefore demonstrate that cAMP is not an important second messenger for ADP-induced platelet aggregation and suggest that another activating pathway, linked to the low affinity ADP receptor present on the platelet surface might be involved in the aggregation process.