Anandamide and neuronal activity in the enteric nervous system: a new potential pharmacological target in controlling intestinal hypersecretion?

Intestinal secretion is regulated, at least in part, by neurons in the submucosal plexus (SMP). The (patho)physiological role of secretomotor neurons in the human SMP is poorly understood. The endogenous cannabinoid (endoCB) system plays a central pathophysiological role in the regulation of gastrointestinal (GI) functions. Anandamide (AEA), the endogenous agonists of CB receptors, also activates the transient receptor potential vanilloid 1 channel (TRPV1). In humans, both signaling mechanisms are present in the ENS but the exact distribution and the extent to which these two systems interact to maintain SMP function are still debated. The endoCB system is over-activated in experimental animal models of hypersecretion. While TRPV1 signaling is involved in the regulation of inflammation and motor functions, no data are available about its role in modulating intestinal secretion. Diarrhea can be a life-threatening GI disease that is characterized by hypersecretion. Abnormal neuronal activation of the ENS is involved in this pathology. The available therapeutic intervention for diarrhea can have important side effects especially in children. As an alternative and more specific strategy, selective drugs that target neuronal hyperactivation could be considered. We aim to evaluate the involvement of endoCB-TRPV1 signaling system 1/ in the modulation of neuronal activity in human SMP and 2/ in the hypersecretory states in human tissues and animal models.

Keywords:Submucosal plexus, Anandamide, Intestinal secretion, Endocannabinoid system, TRPV1, Nerve recording, Human biopsies

Disciplines:Gastro-enterology and hepatology