Long-term peripheral infusion of @entity24661 / @entity24661 promotes @entity1373 , activation and migration of mucosal mast cells in the XXXX gastric fundus.

@entity35 @entity40456 @entity24661 @entity1373
The endogenous neuropeptide @entity24661 / @entity24661 (N/OFQ) modulates behavioral and gastrointestinal responses to stress. Mucosal mast cells (MMCs) are primary mediators of stress-related responses in the gastrointestinal tract. We investigated the influence of N/OFQ and of the N/OFQ peptide (NOP) receptor antagonist, @entity40456 , on MMCs in the @entity35 gastric fundus. N/OFQ was infused subcutaneously for 52 h at 0.1, 1 and 10  g/kg/h and at 1  g/kg/h for 4h, 52 h, 7 days and 14 days via Alzet osmotic minipumps. Density of MMCs and connective tissue mast cells (CTMCs) was assessed histochemically and immunohistochemically. Activation and location of MMCs were assessed by transmission electron microscopy. Contacts between MMCs and nerve elements were assessed by double immunofluorescence. N/OFQ (1  g/kg/h) and @entity40456 (10 and 30  g/kg/h) were infused subcutaneously in the absence and presence of acute cold-restraint stress and density of MMCs was assessed. Peripheral N/OFQ dose-dependently increased the density of MMCs, while not influencing CTMCs. The increasing effect was maintained up to 14 days following continuous infusion, while after termination of the 4-h infusion, the effect declined rapidly. The peptide promoted the activation of MMCs and their migration from the lamina propria toward the epithelial layer. The association between MMCs and nerve fibers was time-dependently down-regulated following N/OFQ infusion. The stress-induced @entity1373 of MMCs was not influenced by N/OFQ and abolished by @entity40456 . @entity40456 alone was ineffective. The present results suggest that endogenous N/OFQ could be considered a potential component of the circuit neuropeptides-mast cells-stress.
