Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation.

“Endocannabinoids are a family of lipid mediators that are 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 (DAGLα), involved in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).

Cannabinoid (CB)1-deficient, wildtype control and C3H/HeJ mice, a genetically constipated model, were used…

DAGLα is expressed in the enteric nervous system and its inhibition reverses 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.”

http://www.ncbi.nlm.nih.gov/pubmed/25684407

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