The endocannabinoid system and gut-brain signalling.
The endocannabinoid system (ECS) consists of cannabinoid receptors, endogenous ligands and the biosynthetic and metabolic enzymes for their formation and degradation. Within the gastrointestinal (GI) tract, the ECS is involved in the regulation of motility, secretion, sensation, emesis, satiety and inflammation. Recent studies examining the ECS in the gut-brain axis have shed new light on this system and reveal many facets of regulation that are amenable to targeting by pharmacological interventions that may prove valuable for the treatment of GI disorders. In particular, it has been shown that endocannabinoid levels in the brain and gut vary according to states of satiety, and in conditions of diarrhea, emesis and inflammation. The expression of cannabinoid (CB)(1) receptors on vagal afferents is controlled by the states of satiety and by gut peptides such as cholecystokinin and ghrelin. Vagal control of gut motor function and emesis is regulated by endocannabinoids in the brainstem acting on CB(1), CB(2) and transient receptor potential vanilloid (TRPV)-1 receptors. The ECS is involved in the modulation of visceral sensation and likely contributes to effects of stress on GI function. This review examines recent developments in our understanding of the ECS in gut-brain signalling.
Storr
Martin A
MA
Department of Medicine, Hotchkiss Brain Institute and Institute of Infection, Immunity and Inflammation, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada.
Sharkey
Keith A
KA
D000818:Animals; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology*; D063388:Endocannabinoids; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; C494484:TRPV1 receptor