title: Anandamide and its congeners inhibit human plasma butyrylcholinesterase. Possible new roles for these endocannabinoids?
abstract: 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 in many 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 1.32-7.48 nM). On the contrary, NAEs are ineffective on AChE kinetic features. On the basis of the X-ray crystallographic structure of human BChE, and by using flexible docking procedures, an hypothesis on the NAE-BChE interaction is formulated by molecular modeling studies. Our results suggest that anandamide and the other acylethanolamides studied could have a role in the modulation of the physiological actions of BChE.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, Perugia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Romani
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rosi
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Fiorini
authors.forename: Irene
authors.initials: I
authors.lastname: Pirisinu
authors.forename: Annarina
authors.initials: A
authors.lastname: Ambrosini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zolese
mesh_terms: D000328:Adult; D001095:Arachidonic Acids / Q000737:chemistry* / Q000502:physiology; D002091:Butyrylcholinesterase / Q000097:blood / Q000737:chemistry*; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000737:chemistry; D018360:Crystallography, X-Ray; D063388:Endocannabinoids; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D053284:Polyunsaturated Alkamides / Q000737:chemistry*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002800:Cholinesterase Inhibitors; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D002091:Butyrylcholinesterase; C078814:anandamide