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GASTROINTESTINAL ENDOCANNABINOID SYSTEM: MULTIFACETED ROLES IN THE HEALTHY AND INFLAMED INTESTINE
Author(s) -
Smid Scott D
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05016.x
Subject(s) - endocannabinoid system , anandamide , cannabinoid receptor , lipid signaling , immune system , inflammation , motility , prostaglandin , cannabinoid , biology , medicine , neuroscience , pharmacology , immunology , receptor , endocrinology , microbiology and biotechnology , agonist
SUMMARY1 The endogenous cannabinoid (endocannabinoid) system is emerging as a key modulator of intestinal physiology, influencing motility, secretion, epithelial integrity and immune function in the gut, in addition to influencing satiety and emesis. 2 Accumulating evidence suggests that the endocannabinoid system may play a pivotal role in the pathophysiology of gastrointestinal disease, particularly in the light of recent studies demonstrating an effect of endocannabinoids on the development of experimental inflammation and linkages with functional clinical disorders characterized by altered motility. 3 The predominant endocannabinoids, anandamide and 2‐arachidonoylglycerol, not only mediate their effects via two recognized cannabinoid receptor subtypes, namely CB 1 and CB 2 , but emerging evidence now shows they are also substrates for cyclo‐oxygenase (COX)‐2, generating a distinct and novel class of prostaglandin ethanolamides (prostamides) and prostaglandin glycerol esters. These compounds are bioactive and may mediate an array of biological effects distinct to those of conventional prostanoids. 4 The effects of prostamides on gastrointestinal motility, secretion, sensation and immune function have not been characterized extensively. Prostamides may play an important role in gastrointestinal inflammation, particularly given the enhanced expression of both COX‐2 and endocannabinoids that occurs in the inflamed gut. 5 Further preclinical studies are needed to determine the therapeutic potential of drugs targeting the endocannabinoid system in functional and inflammatory gut disorders, to assist with the determination of feasibility for clinical translation.