KSU Biological Sciences Seminar - The endocannabinoid system, its extension to the endocannabinoidome, and the relationships of both with the gut microbiome
The endocannabinoid system, its extension to the endocannabinoidome, and the relationships of both with the gut microbiome
Vincenzo Di Marzo, PhD, Professor and Canada Excellence Research Chair, Université Laval
For several decades, and starting some 25 years from its discovery, the only plant cannabinoid (phytocannabinoid) with an established mechanism for its pharmacological actions has been D9-tetrahydrocannabinol (THC). To THC are ascribed the most important euphoric and psychotropic effects of recreational preparations (e.g. marijuana, hashish) obtained from those varieties of Cannabis sativa that are rich in this compound. These effects on the central nervous system are now known to be due to THC capability of activating endogenous G-protein-coupled receptors (GPCRs) that are among the most abundant such proteins in the mammalian brain: the type-1 cannabinoid (CB1) receptors. THC also activates another GPCR, the type-2 cannabinoid (CB2) receptors, through which it produces instead anti-inflammatory and immune-modulatory actions. The discovery of CB1 and CB2 receptors led to the finding of their endogenous agonists, later named endocannabinoids: N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoyl-glycerol (2-AG). The chemical signaling system composed of CB1 and CB2 receptors, the two endocannabinoids and the anabolic and catabolic enzymes regulating endocannabinoid levels, became known as the endocannabinoid system.
Later, an expanded endocannabinoid system, including several non-endocannabinoid long chain fatty acid amides and esters, among which: a) the congeners of anandamide and 2-AG, b) the N-acyl-aminoacids, c) the N-acyl-neurotransmitters and d) the primary fatty acid amides, has been discovered. These lipid mediators often share with the two endocannabinoids biosynthetic and/or inactivating enzymes, but not necessarily their receptors, which instead include orphan GPCRs, ligand-activated ion channels and peroxisome proliferator-activated nuclear receptors (PPARs). These small molecules, therefore, should not be considered endocannabinoids sensu stricto, but instead as endocannabinoid-like mediators, and this expanded endocannabinoid system is becoming known as the endocannabinoidome.
The endocannabinoidome is involved in almost all aspects of mammalian physiology and pathology, and recent work from my and other laboratories have highlighted how this complex signalling system is modulated by, and in turn modulates, another fundamental player in several physiopathological conditions: the gut microbiome. I will present data on the endocannabinoidome-gut microbiome axis and its emerging importance in obesity and neuropsychiatric disorders.
Contact: Email dcostel3@kent.edu for link and/or to be added to the BSCI seminar mailing list
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