HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/G1255    most recent 90500.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Duncan, M. Articles by Sharkey, K. A. Search for Related Content PubMed PubMed Citation Articles by Duncan, M. Articles by Sharkey, K. A.

NEUROREGULATION AND MOTILITY

Distribution and function of monoacylglycerol lipase in the gastrointestinal tract

¹Hotchkiss Brain Institute and Snyder Institute of Infection, Immunity and Inflammation, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; ²School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham Medical School, Nottingham, United Kingdom; ³Department of Physiological Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany; and ⁴Department of Pharmacology, University of California, Irvine, California

Submitted 18 August 2008 ; accepted in final form 17 October 2008

The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined.

endocannabinoids; enteric nervous system; URB602; 2-arachidonoyl glycerol