Neuropeptide S Reduces Gut Motility in Rats and Humans

The actions of NPS on intestinal motility and duodenal mucosal barrier function in anaesthetized rat in vivo and human circular muscle strips in vitro were elucidated in this study. A segment of the proximal duodenum or descending colon with an intact blood supply of male Sprague‐Dawley rat was perfused in situ . The effects of intravenous (i.v.) administration of neuropeptide S (NPS) and N G ‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated on intestinal motility and duodenal mucosal paracellular permeability. The influence of NPS on ethanol‐induced changes of duodenal mucosal bicarbonate secretion (DBS) was studied. Normal human circular colonic muscle strips were studied in organ bath. Tension changes were measured after NPS administration, NPS challenge with L‐NAME, tetrodotoxin (TTX) or stimulated with EFS. Values are mean ± SEM, compared by 1‐ or 2‐way ANOVA or paired t test when appropriate. NPS decreases both small intestinal and colonic motility but increases duodenal paracellular permeability. Pre‐treating animals with the non‐selective NOS inhibitor L‐NAME abolished the effect of NPS on duodenal motility but not on permeability. NPS reduces ethanol‐induced increases in DBS. In the human colonic smooth muscle strip, NPS dampened contractility with or without electrical field stimulation, which abolished by administration of L‐NAME and TTX. NPS inhibits gastrointestinal motility in animal and man, most likely via a neural nitric oxide (NO) release. To this end, NPS increases paracellular permeability may represent an early step of inflammatory response.