br Author contributions Animal experiments real time PCR and

Author contributions Animal experiments, real time PCR and western blots were performed at the Department of Physiology, CIMUS, University of Santiago de Compostela and Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigaciones Biomédicas (IMIBIC) / Reina Sofia University Hospital / University of Cordoba. Mass spectrometry was performed at the Rowett Institute of Nutrition and Health, University of Aberdeen.
Since the discovery that effects of cannabinoids are due to actual ligand–receptor interaction and not to some kind of non-specific membrane disturbance, the cannabinoid (CB) receptors, a family of seven-transmembrane spanning (7TM) G protein-coupled receptors (GPCRs), have become the focus of intense research. Over the years it has become obvious that the diverse biological effects of cannabinoids (natural cannabinoids, synthetic cannabinoids and endocannabinoids) cannot be explained only by the actions of the two established CB receptors (CB1 and CB2), but that cannabinoid activity is mediated also by various ionotropic receptors and uncharacterized GPCRs (reviewed in []).
Is there a functional role for GPR55 in the GI tract? CB1 receptors are known to be involved in several motor functions of the GI tract like esophageal sphincter relaxation and gastric emptying (reviewed in [31]) while CB2 receptors show no involvement in motility, at least not in physiological conditions. However, data have accumulated showing that CB2 may come into power in situations during intestinal inflammation [32, 33, 34•, 35•]. Since GPR55 can be activated by endogenous and exogenous cannabinoids we discuss in the following paragraphs the possibility that GPR55 may have a functional role in GI physiology and pathophysiology.
Concluding remarks Despite the paucity of studies on the role of GPR55 in the GI tract, we can positively assume that GPR55 is involved in the regulation of GI functions under physiological and pathophysiological conditions. The expression of GPR55 in PCI32765 areas known to govern energy household and bowel functions as well as in enteric epithelial cells and enteric neurons suggests that GPR55 is likely involved in GI processes such as motility and possibly secretion. Its upregulation in gut tissue after systemic inflammation indicates that GPR55 may play a role in pathophysiological mechanisms of intestinal inflammation and this seems to hold true for experimental inflammatory conditions of different kinds. Additionally, the presence of GPR55 in mechanoreceptors raises the intriguing possibility that GPR55 may have a role in the regulation of gut motility via extrinsic nerve fibers, provided that GPR55 is located on mechanoreceptors innervating the GI tract. It will be interesting to find out whether GPR55 interacts with classical CB receptors in response to endocannabinoids in the GI tract and in brain areas affecting GI functions and whether GPR55 may have a role in disorders of food intake. Future studies involving selective agonists, antagonists and possibly GPR55−/− mice are warranted to follow the promising evidence that GPR55 is crucially involved in the regulation of GI function in health and disease and to facilitate possible translation into future treatments of GI diseases.
Disclosures
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as:
Acknowledgments RS is supported by grants from the Austrian Science Fund (FWF P 22771), Austrian National Bank (OeNB 14429) and the Franz Lanyar Foundation (351). MS is supported by the Deutsche Forschungsgemeinschaft (DFG).
Introduction The prevalence of functional gastrointestinal disorders (FGID), such as irritable bowel syndrome (IBS), is currently estimated at 10–20%. It has a tendency to increase, in particular in the societies adopting Western style of living (Philpott et al., 2011). Symptoms manifested by FGID patients – predominantly altered motility patterns, stool inconsistency and bloating are not life-threatening, but are often associated with abdominal pain and have a negative impact on life quality. Thus, such disturbances have become a heavy economic burden due to increased work absenteeism, as well as increased use of health care services (Drossman, 2006). Current understanding of the pathogenesis of FGID and their clinical resolution are unsatisfactory. So far, hypotheses suggest low grade inflammation (Mayer and Collins, 2002; Philpott et al., 2011), food allergy (Atkinson et al., 2004) or disturbances in the bi-directional communication between the gut and the central nervous system (CNS) (Fichna and Storr, 2012). New therapeutic strategies, alleviating motility disturbances and pain without adverse, mainly related to the central nervous system side effects are therefore urgently needed.