Anandamide and its congeners inhibit human plasma butyrylcholinesterase. Possible new roles for these endocannabinoids?

Butyrylcholinesterase (BChE), a serine hydrolase biochemically related to the cholinergic enzyme Acetylcholinesterase (AChE), is found in many mammalian tissues, such as serum and central nervous system, but its physiological role is still unclear. BChE is an important human plasma esterase, where it has detoxifying roles. Furthermore, recent studies suggest that brain BChE can have a role in Alzheimer’s disease (AD). The endocannabinoid arachidonoylethanolamide (anandamide) and other acylethanolamides (NAEs) are almost ubiquitary molecules and are physiologically present inmany tissues, including blood and brain, where they show neuroprotective and anti-inflammatory properties. This paper demonstrates that they are uncompetitive (oleoylethanolamide and palmitoylethanolamide) or non competitive (anandamide) inhibitors of BChE (Ki in the range 1.32e7.48 nM).Onthe contrary,NAEs are ineffective onAChE kinetic features. On the basis of the Xray crystallographic structure of human BChE, and by using flexible docking procedures, an hypothesis on the NAE-BChE interaction is formulated bymolecularmodeling studies. Our results suggest that anandamide and the other acylethanolamides studied could have a role in the modulation of the physiological actions of BChE. 2011 Elsevier Masson SAS. All rights reserved.