{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:18:48Z","timestamp":1789586328230,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T00:00:00Z","timestamp":1438214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Funds (FWF)","award":["P21296"],"award-info":[{"award-number":["P21296"]}]},{"name":"Austrian Science Funds (FWF)","award":["P22771"],"award-info":[{"award-number":["P22771"]}]},{"name":"Austrian Science Funds (FWF)","award":["P25633"],"award-info":[{"award-number":["P25633"]}]},{"name":"DK Molecular Enzymology","award":["W901-B05 DK"],"award-info":[{"award-number":["W901-B05 DK"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"Background and Purpose<\/jats:title>Monoglyceride lipase (MGL<\/jats:styled-content>) degrades 2\u2010arachidonoyl glycerol (2\u2010AG<\/jats:styled-content>), an endogenous agonist of cannabinoid receptors (CB<\/jats:styled-content>1\/2<\/jats:sub>). Because the CB<\/jats:styled-content>1<\/jats:sub> receptor is involved in the control of gut function, we investigated the effects of pharmacological inhibition and genetic deletion of MGL<\/jats:styled-content> on intestinal motility. Furthermore, we determined whether defective 2\u2010AG<\/jats:styled-content> degradation affects \u03bc\u2010opioid receptor (\u03bc receptor) signalling, a parallel pathway regulating gut motility.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Gut motility was investigated by monitoring E<\/jats:styled-content>vans B<\/jats:styled-content>lue transit and colonic bead propulsion in response to MGL<\/jats:styled-content> inhibition and CB<\/jats:styled-content>1<\/jats:sub> receptor or \u03bc receptor stimulation. Ileal contractility was investigated by electrical field stimulation. CB<\/jats:styled-content>1<\/jats:sub> receptor expression in ileum and colon was assessed by immunohistochemical analyses.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Pharmacological inhibition of MGL<\/jats:styled-content> slowed down whole gut transit in a CB<\/jats:styled-content>1<\/jats:sub> receptor\u2010dependent manner. Conversely, genetic deletion of MGL<\/jats:styled-content> did not affect gut transit despite increased 2\u2010AG<\/jats:styled-content> levels. Notably, MGL<\/jats:styled-content> deficiency caused complete insensitivity to CB<\/jats:styled-content>1<\/jats:sub> receptor agonist\u2010mediated inhibition of whole gut transit and ileal contractility suggesting local desensitization of CB<\/jats:styled-content>1<\/jats:sub> receptors. Accordingly, immunohistochemical analyses of myenteric ganglia of MGL<\/jats:styled-content>\u2010deficient mice revealed that CB<\/jats:styled-content>1<\/jats:sub> receptors were trapped in endocytic vesicles. Finally, MGL<\/jats:styled-content>\u2010deficient mice displayed accelerated colonic propulsion and were hypersensitive to \u03bc receptor agonist\u2010mediated inhibition of colonic motility. This phenotype was reproduced by chronic pharmacological inhibition of MGL<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>Constantly elevated 2\u2010AG<\/jats:styled-content> levels induce severe desensitization of intestinal CB<\/jats:styled-content>1<\/jats:sub> receptors and increased sensitivity to \u03bc receptor\u2010mediated inhibition of colonic motility. These changes should be considered when cannabinoid\u2010based drugs are used in the therapy of gastrointestinal diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13224","type":"journal-article","created":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T09:55:41Z","timestamp":1434362141000},"page":"4419-4429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Monoglyceride lipase deficiency causes desensitization of intestinal cannabinoid receptor type 1 and increased colonic \u03bc\u2010opioid receptor sensitivity"],"prefix":"10.1111","volume":"172","author":[{"given":"U","family":"Taschler","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T O","family":"Eichmann","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz Graz 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