Activation of rabbit blood platelets by anandamide through its cleavage into arachidonic acid

Anandamide (ANA), a cannabinoid receptor ligand, stimulated platelet aggreg ation at concentrations similar to those of arachidonic acrid (AA). The agg regating effect of ANA was inhibited by aspirin but not by SR-141716, a can nabinoid receptor antagonist. In addition, HU-210, a cannabinoid receptor a gonist, failed to induce platelet activation. Radiolabelling. experiments s howed that exogenous ANA was cleaved by platelets into AA through a phenylm ethylsulfonyl fluoride (PMSF)-sensitive pathway. In agreement, PMSF was sho wn to abolish the aggregating effect of ANA, In conclusion, ANA is able to induce platelet activation via its cleavage by a PMSF-sensitive amidase act ivity, leading to the release of AA which in turn activates platelets. (C) 2000 Federation of European Biochemical Societies.