ArticleBritish journal of pharmacology2015
Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation.
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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Shaoyao Gancao decoction alleviates functional constipation by inhibitingFrontiers in cellular and infection microbiology · 2025Article
- Article
- Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.British journal of cancer · 2024Review
- Cannabinoids and the Gastrointestinal Tract.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Review
- Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism.Veterinary sciences · 2022Article
- The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism.Frontiers in cellular neuroscience · 2022Review
- Pharmacology, Clinical Effects, and Therapeutic Potential of Cannabinoids for Gastrointestinal and Liver Diseases.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2021Review
- Thymol modulates the endocannabinoid system and gut chemosensing of weaning pigs.BMC veterinary research · 2020Article
- The Manufacturing Process of Kiwifruit Fruit Powder with High Dietary Fiber and Its Laxative Effect.Molecules (Basel, Switzerland) · 2019Article
- Spinal Cord Injury in Rats Dysregulates Diurnal Rhythms of Fecal Output and Liver Metabolic Indicators.Journal of neurotrauma · 2019Article
- Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.Frontiers in pharmacology · 2019Article
- Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.Neurogastroenterology and motility · 2018Review
- Endocannabinoid-related compounds in gastrointestinal diseases.Journal of cellular and molecular medicine · 2018Review
- The gastrointestinal tract - a central organ of cannabinoid signaling in health and disease.Neurogastroenterology and motility · 2016Review
- Cannabinoids and GI Disorders: Endogenous and Exogenous.Current treatment options in gastroenterology · 2016Review
- The Role of the Endocannabinoid System in the Brain-Gut Axis.Gastroenterology · 2016Review
- Endocannabinoids in the Gut.Cannabis and cannabinoid research · 2016Article
- Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation.Current neuropharmacology · 2016Review
- DAG tales: the multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling.Cellular and molecular life sciences : CMLS · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
background and purposeEndocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase-α (DAGLα), which is involved in biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). EXPERIMENTAL APPROACH: Cannabinoid CB1 receptor-deficient, wild-type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGLα in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM-188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry. KEY
resultsDAGLα was expressed throughout the GI tract. In the intestine, unlike DAGLβ, DAGLα immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2-AG was elevated while inhibiting DAGL normalized 2-AG levels. CONCLUSIONS AND IMPLICATIONS: DAGLα was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2-AG and CB1 receptor-mediated mechanisms. Our data suggest that DAGLα inhibitors may be promising candidates for the treatment of constipation.
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Registered trials
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.