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

• Published in: Biochimie 2011-09, Vol.93 (9), p.1584-1591
• Main Authors: Romani, Rita, Galeazzi, Roberta, Rosi, Gabriella, Fiorini, Rosamaria, Pirisinu, Irene, Ambrosini, Annarina, Zolese, Giovanna
• Format: Article
• Language: English
• Subjects: Adult; Anandamide; Arachidonic Acids - chemistry; Arachidonic Acids - physiology; Butyrylcholinesterase - blood; Butyrylcholinesterase - chemistry; Cannabinoid Receptor Modulators - chemistry; Cannabinoid Receptor Modulators - physiology; Cholinesterase Inhibitors - chemistry; Crystallography, X-Ray; Endocannabinoids; Human plasma butyrylcholinesterase; Humans; Kinetic studies; Kinetics; Male; Middle Aged; Oleoylethanolamide; Palmitoylethanolamide; Polyunsaturated Alkamides - chemistry
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2011.05.024

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. ► Effect of some endocannabinoids on cholinesterases activity is studied. ► Anandamide inhibits purified butyrylcholinesterase. ► Other anandamide congeners inhibit butyrylcholinesterase. ► Endocannabinoids-butyrylcholinesterase interactions are studied by docking technique.