Anandamide and its congeners inhibit human plasma butyrylcholinesterase. Possible new roles for these endocannabinoids?
| Autor: | Giovanna Zolese, Rosamaria Fiorini, Rita Romani, Roberta Galeazzi, Irene Pirisinu, Gabriella Rosi, Annarina Ambrosini |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Polyunsaturated Alkamides Arachidonic Acids Pharmacology Crystallography X-Ray Biochemistry chemistry.chemical_compound Oleoylethanolamide Cannabinoid Receptor Modulators Humans Palmitoylethanolamide Butyrylcholinesterase Cholinesterase biology Human plasma butyrylcholinesterase Kinetic studies Anandamide Oleoylethanolamide Palmitoylethanolamide Serine hydrolase General Medicine Anandamide Middle Aged Endocannabinoid system Acetylcholinesterase Human plasma butyrylcholinesterase Kinetics chemistry biology.protein Kinetic studies Cholinesterase Inhibitors Endocannabinoids |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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