Anandamide activates human platelets through a pathway independent of the arachidonate cascade

Anandamide (arachidonoylethanolamide, AnNH) is shown to activate human plat elets, a process which was not inhibited by acetylsalicylic acid (aspirin), Unlike AnNH, hydroperoxides generated thereof by lipoxygenase activity, an d the congener (13-hydroxy)linoleoylethanolamide, were unable to activate p latelets, though they counteracted AnNH-mediated stimulation. On the other hand, palmitoylethanolamide neither activated human platelets nor blocked t he AnNH effects. AnNH inactivation by human platelets was afforded by a hig h-affinity transporter, which was activated by nitric oxide-donors up to 22 5% of the control. The internalized AnNH could thus be hydrolyzed by a fatt y acid amide hydrolase (FAAH), characterized here for the first time, (C) 1 999 Federation of European Biochemical Societies.