CAMP IS NOT AN IMPORTANT MESSENGER FOR ADP-INDUCED PLATELET-AGGREGATION

In rat platelets, basal cAMP level did not vary significantly during A DP-induced aggregation. In the same conditions, no variation in the cA MP content was observed in platelets from rats treated with clopidogre l, 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 s trongly inhibited SQ 22536 (500 mu M), an inhibitor of adenylyl cyclas e, strongly reduced the cAMP content of both control and treated plate lets but did not reverse the anti-aggregating activity of clopidogrel, showing that inhibition of ADP-induced adenylyl cyclase down-regulati on in treated platelets was not responsible for the anti-aggregating e ffect of clopidogrel. Similar results were obtained in rabbit platelet s. These results therefore demonstrate that cAMP is not an important s econd messenger for ADP-induced platelet aggregation and suggest that another activating pathway, linked to the low affinity ADP receptor pr esent on the platelet surface might be involved in the aggregation pro cess.