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Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation.

ABSTRACT: Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduces the gastric mucosal lesions induced by NSAIDs in a CB1 receptor-dependent fashion. Dual inhibition of FAAH and cyclooxygenase enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal inflammation. Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors exerts also multiple beneficial effects. Namely, activation of both CB receptors was shown to ameliorate intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea. In addition, CB1 receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus, experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.

SUBMITTER: Gyires K

PROVIDER: S-EPMC5333598 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation.

Gyires Klára K Zádori Zoltán S ZS

Current neuropharmacology 20160101 8

Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gas ...[more]

PMID: 26935536

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Project description:Background & aimsColonic diverticulosis has been reported to be associated with low-grade mucosal inflammation, possibly leading to chronic gastrointestinal symptoms. However, there is poor evidence for this association. We aimed to determine mucosal inflammation and whether diverticula are associated with chronic gastrointestinal symptoms. We explored whether inflammation was present among symptomatic participants with and without diverticula.MethodsWe analyzed data from a prospective study of 619 patients undergoing a screening colonoscopy from 2013 through 2015 at the University of North Carolina Hospital in Chapel Hill, North Carolina. Among our participants, 255 (41%) had colonic diverticula. Colonic mucosal biopsy specimens were analyzed for levels of interleukin 6 (IL6), IL10, and tumor necrosis factor messenger RNAs by quantitative reverse-transcriptase polymerase chain reaction, and numbers of immune cells (CD4+, CD8+, CD57+, and mast cell tryptase) by immunohistochemistry. Gastrointestinal symptoms were assessed using Rome III criteria. Proportional odds models were used to estimate odds ratios (ORs) and 95% confidence interval (CIs).ResultsAfter adjustment for potential confounders, there was no association between diverticulosis and tumor necrosis factor (OR, 0.85; 95% CI, 0.63-1.16), and no association with CD4+ cells (OR, 1.18; 95% CI, 0.87-1.60), CD8+ cells (OR, 0.97; 95% CI, 0.71-1.32), or CD57+ cells (OR, 0.80; 95% CI, 0.59-1.09). Compared with controls without diverticulosis, biopsy specimens from individuals with diverticulosis were less likely to express the inflammatory cytokine IL6 (OR, 0.59; 95% CI, 0.36-0.96). There was no association between diverticulosis and irritable bowel syndrome (OR, 0.53; 95% CI, 0.26-1.05) or chronic abdominal pain (OR, 0.68; 95% CI, 0.38-1.23). There was no evidence for inflammation in patients with symptoms when patients with vs without diverticulosis were compared.ConclusionsWe found no evidence that colonic diverticulosis is associated with mucosal inflammation or gastrointestinal symptoms. Among patients with symptoms and diverticula, we found no mucosal inflammation.

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Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation.

Publications

Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation.

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