Anandamide activates human platelets through a pathway independent of the arachidonate cascade.
Anandamide (arachidonoylethanolamide, AnNH) is shown to activate human platelets, a process which was not inhibited by acetylsalicylic acid (aspirin). Unlike AnNH, hydroperoxides generated thereof by lipoxygenase activity, and the congener (13-hydroxy)linoleoylethanolamide, were unable to activate platelets, though they counteracted AnNH-mediated stimulation. On the other hand, palmitoylethanolamide neither activated human platelets nor blocked the AnNH effects. AnNH inactivation by human platelets was afforded by a high-affinity transporter, which was activated by nitric oxide-donors up to 225% of the control. The internalized AnNH could thus be hydrolyzed by a fatty acid amide hydrolase (FAAH), characterized here for the first time.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Bari
M
M
Menichelli
A
A
Del Principe
D
D
Agrò
A F
AF
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000577:Amides; D000581:Amidohydrolases / Q000097:blood / Q000235:genetics; D000595:Amino Acid Sequence; D016718:Arachidonic Acid / Q000097:blood / Q000494:pharmacology; D001095:Arachidonic Acids / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002186:Cannabinoids / Q000097:blood / Q000494:pharmacology*; D063388:Endocannabinoids; D004983:Ethanolamines; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010169:Palmitic Acids / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases
D000244:Adenosine Diphosphate; D000577:Amides; D000581:Amidohydrolases; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D002118:Calcium; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C005958:palmidrol; C078814:anandamide