Review article: endocannabinoids and their receptors in the enteric nervous system.
The therapeutic actions of cannabinoids have been known for centuries. In the last 25 years this area of research has grown exponentially with the discovery of specific cannabinoid receptors and endogenous ligands. In the enteric nervous system of gastrointestinal tract, cannabinoid receptors are located on enteric nerve terminals where they exert inhibitory actions on neurotransmission to reduce motility and secretion. Endogenous cannabinoids are present in the enteric nervous system, as are the degradative enzymes necessary to inhibit their action. The cellular mechanism of action of endocannabinoids has not been established in the enteric nervous system. Endocannabinoids not only act at cannabinoid receptors, but potentially also at vanilloid and 5-HT3 receptors, both of which are expressed in the gastrointestinal tract. The interactions between endocannabinoids and these other important receptor systems have not been extensively investigated. A greater understanding of the endocannabinoid system in the enteric nervous system could lead to advances with important therapeutic potential in the treatment of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, secretory diarrhoea and gastro-oesophageal reflux disease.