The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity.
Crohn's disease and ulcerative colitis are two major forms of inflammatory bowel diseases (IBD), which are chronic inflammatory disorders of the gastrointestinal tract. These pathologies are currently under investigation to both unravel their etiology and find novel treatments. Anandamide and 2-arachidonoylglycerol are endogenous bioactive lipids that bind to and activate the cannabinoid receptors, and together with the enzymes responsible for their biosynthesis and degradation [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)] constitute the endocannabinoid system (ECS). The ECS is implicated in gut homeostasis, modulating gastrointestinal motility, visceral sensation, and inflammation, as well as being recently implicated in IBD pathogenesis. Numerous subsequent studies investigating the effects of cannabinoid agonists and endocannabinoid degradation inhibitors in rodent models of IBD have identified a potential therapeutic role for the ECS.
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Av. E. Mounier, 72, B1.72.01, 1200 Bruxelles, Belgium.
Mireille
M
Alhouayek
Giulio G
GG
Muccioli
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005989:Glycerides / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D008994:Monoacylglycerol Lipases; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide