ABSTRACTEndocannabinoids are an emerging class of cannabinomimetic lipid mediators, which are endogenous ligands for both the brain-type (CB1-R) and the spleen-type (CB2-R) cannabinoid receptors. Anandamide (arachidonoylethanolamide, AEA) is a prominent endocannabinoid . A specific AEA transporter has been recently identified, which allows the import and intacellular degradation of this lipid by the enzyme anandimide hydrolase (fatty acid amide hydrolase, FAAH) Here, the biochemical properties of AEA tansporter and FAAH in human cells will be reviewed. The ability to take up AEA and to degrade it to arachidonic acid and ethanolamine was studied in neuroblastoma CHP100 and lymphoma U937 cell lines. Both AEA transporter and FAAH were found and characterized also in human platelets. Kinetic parameters of AEA uptake were as follows : apparent Km of 0.20, 0.13 and 0.20 µM, and apparent Vmax of 30, 140 and 22 pmol.min –1.mg protein –1 , for CHP 100, U937 and platelets respectively. On the other hand, FAAH activity showed apparent Km of 6.5, 6.5 and 10 µM, and apparent Vmax of 32, 520 and 270 pmol.min-1.mg protein-1, in CHP100, U937and platelets respectively. Remarkably, nitric oxide-releasing compounds enhanced AEA uptake in all human cells tested. These findings will be discussed in the light of the multiple roles of endocannabinoids in human pathophysiology.
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