ArticleBritish journal of pharmacology2015
Monoglyceride lipase deficiency causes desensitization of intestinal cannabinoid receptor type 1 and increased colonic μ-opioid receptor sensitivity.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Protective Effects of Monoacylglycerol Lipase Inhibition in Rats with Severe Acute Pancreatitis and Its Possible MechanismEndocrine, metabolic & immune disorders drug targets · 2026Article
- Negative allosteric modulation of CBNeuropharmacology · 2024Article
- SGIP1 in axons prevents internalization of desensitized CB1R and modifies its function.Frontiers in neuroscience · 2023Review
- Review
- Chronic Cannabis Intoxication and Propofol-Induced Salivation: Causes and Considerations.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Article
- The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism.Frontiers in cellular neuroscience · 2022Review
- Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.Frontiers in pharmacology · 2022Article
- Role of the Endocannabinoid System in the Regulation of Intestinal Homeostasis.Cellular and molecular gastroenterology and hepatology · 2022Review
- The Endocannabinoid Analgesic Entourage Effect: Investigations in Cultured DRG Neurons.Journal of pain research · 2022Article
- Protective effect of cannabinoids on gastric mucosal lesions induced by water immersion restrain stress in rats.Iranian journal of basic medical sciences · 2021Article
- Role of the Endocannabinoid System in the Adipose Tissue with Focus on Energy Metabolism.Cells · 2021Review
- Monoacylglycerol lipase deficiency in the tumor microenvironment slows tumor growth in non-small cell lung cancer.Oncoimmunology · 2021Article
- Article
- Article
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Cannabis, Cannabinoids, and the Endocannabinoid System-Is there Therapeutic Potential for Inflammatory Bowel Disease?Journal of Crohn's & colitis · 2019Review
- Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.Pharmacology & therapeutics · 2017Review
- Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice.Oncotarget · 2017Article
- The gastrointestinal tract - a central organ of cannabinoid signaling in health and disease.Neurogastroenterology and motility · 2016Review
- Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide-induced Neuroinflammation.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeMonoglyceride lipase (MGL) degrades 2-arachidonoyl glycerol (2-AG), an endogenous agonist of cannabinoid receptors (CB1/2 ). Because the CB1 receptor is involved in the control of gut function, we investigated the effects of pharmacological inhibition and genetic deletion of MGL on intestinal motility. Furthermore, we determined whether defective 2-AG degradation affects μ-opioid receptor (μ receptor) signalling, a parallel pathway regulating gut motility. EXPERIMENTAL APPROACH: Gut motility was investigated by monitoring Evans Blue transit and colonic bead propulsion in response to MGL inhibition and CB1 receptor or μ receptor stimulation. Ileal contractility was investigated by electrical field stimulation. CB1 receptor expression in ileum and colon was assessed by immunohistochemical analyses. KEY
resultsPharmacological inhibition of MGL slowed down whole gut transit in a CB1 receptor-dependent manner. Conversely, genetic deletion of MGL did not affect gut transit despite increased 2-AG levels. Notably, MGL deficiency caused complete insensitivity to CB1 receptor agonist-mediated inhibition of whole gut transit and ileal contractility suggesting local desensitization of CB1 receptors. Accordingly, immunohistochemical analyses of myenteric ganglia of MGL-deficient mice revealed that CB1 receptors were trapped in endocytic vesicles. Finally, MGL-deficient mice displayed accelerated colonic propulsion and were hypersensitive to μ receptor agonist-mediated inhibition of colonic motility. This phenotype was reproduced by chronic pharmacological inhibition of MGL. CONCLUSION AND IMPLICATIONS: Constantly elevated 2-AG levels induce severe desensitization of intestinal CB1 receptors and increased sensitivity to μ receptor-mediated inhibition of colonic motility. These changes should be considered when cannabinoid-based drugs are used in the therapy of gastrointestinal diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.