Gastroenterology

CB2 receptor may exert an important inhibitory effect in stress-induced colonic hypermotility by modulating NO synthesis through p38 mitogen-activated protein kinase signaling. AM1241 could be used as a potential drug to treat disorders with colonic hypermotility.

Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal acid reflux, and are triggered by postprandial gastric distention. Stimulation of GABAB receptors potently inhibits triggering of TLESR by gastric loads. The functional similarity between GABAB and cannabinoid receptors (CBRs) prompted us to study the role of CBRs on mechanisms of gastric distention-induced TLESRs. Methods: Gastric nutrient infusion and air insufflation was performed during gastroesophageal manometry in conscious dogs. The effects of the CBR agonist WIN 55,212-2 were assessed alone and in combination with the CBR1 antagonist SR141716A or the CBR2 antagonist SR144528. The effects of WIN 55,212-2 were also studied on firing of gastric vagal mechanosensitive afferents in an isolated preparation of ferret stomach. Results: WIN 55,212-2 (57 nmol/kg) inhibited the occurrence of TLESR after gastric loads by 80% (P < 0.01). The latency to the first TLESR after the load was prolonged (P < 0.001), and the occurrence of swallowing was reduced (P < 0.05). The CBR1 antagonist SR141716A reversed the effects of WIN 55,212-2, whereas the CBR2 antagonist SR144528 did not. The CBR1 antagonist alone increased occurrence of TLESR (P < 0.05). The responses of gastric vagal mechanoreceptors to distention were unaffected by WIN 55,212-2 at a concentration of 3 μmol/L. Conclusions: Exogenous and endogenous activation of the CBR1 receptor inhibits TLESRs. The effects of CBR1 are not mediated peripherally on gastric vagal afferents, and therefore are most likely in the brain stem.

Revealing the multifocal mechanisms affecting cross-talk between Clostridium perfringens pathogenesis and the host response is an urgent need in the poultry industry. Herein, the activity of Cannabis sativa-derived cannabidiol (CBD) and selenium nanoparticles (Nano-Se) in modulating the host response to Clostridium perfringens challenge was investigated in broiler chickens subjected to a mild infection model. The infected chickens exhibited no clinical manifestations, confirming the potential hazard of pathogen transmission to the food chain in the commercial sector. However, both CBD and Nano-Se affected the responses of chickens to C. perfringens challenge. The beneficial actions of both agents were manifested in the upregulated expression of genes determining gut barrier function. Both CBD and Nano-Se promoted shifts in gut bacterial enzyme activity to increased energy uptake in challenged chickens and upregulated potential collagenase activity. There was no opposite effect of CBD and Nano-Se in mediating the host response to challenge, whereas an additive effect was evidenced on the upregulation of gene determining gut integrity. Collectively, these findings indicate that understanding the action mechanisms of CBD and Nano-Se is of great interest for developing a preventive strategy for C. perfringens infection in broilers.

Colic is a common digestive disorder in horses and one of the most urgent problems in equine medicine. A growing body of literature has indicated that the activation of cannabinoid receptors could exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity. The localisation of cannabinoid and cannabinoid-related receptors in the intestine of the horse has not yet been investigated. The purpose of this study was to immunohistochemically localise the cellular distribution of canonical and putative cannabinoid receptors in the ileum of healthy horses. Distal ileum specimens were collected from six horses at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and three putative cannabinoid-related receptors: nuclear peroxisome proliferator-activated receptor-alpha (PPARα), transient receptor potential ankyrin 1 and serotonin 5-HT1a receptor (5-HT1aR). Cannabinoid and cannabinoid-related receptors showed a wide distribution in the ileum of the horse. The epithelial cells showed immunoreactivity for CB1R, CB2R and 5-HT1aR. Lamina propria inflammatory cells showed immunoreactivity for CB2R and 5-HT1aR. The enteric neurons showed immunoreactivity for CB1R, transient receptor potential ankyrin 1 and PPARα. The enteric glial cells showed immunoreactivity for CB1R and PPARα. The smooth muscle cells of the tunica muscularis and the blood vessels showed immunoreactivity for PPARα. The present study represents a histological basis which could support additional studies regarding the distribution of cannabinoid receptors during gastrointestinal inflammatory diseases as well as studies assessing the effects of non-psychotic cannabis-derived molecules in horses for the management of intestinal diseases.