Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide
2015 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 8, G625-G634 p.Article in journal (Refereed) Published
Neuropeptide S (NPS) receptor (NPSR1) polymorphisms are associated with enteral dysmotility and inflammatory bowel disease (IBD). This study investigated the role of NPS in conjunction with nitrergic mechanisms in the regulation of intestinal motility and mucosal permeability. In rats, small intestinal myoelectric activity and luminal pressure changes in small intestine and colon, along with duodenal permeability were studied. In human intestine, NPS and NPSR1 were localized by immunostaining. Pre- and postprandial plasma NPS was measured by ELISA in healthy and active IBD humans. Effects and mechanisms of NPS were studied in human intestinal muscle strips. In rats, NPS 100-4000 pmol/kg·min had effects on the small intestine and colon. Low doses of NPS increased myoelectric spiking (p<0.05). Higher doses reduced spiking and prolonged the cycle length of the migrating myoelectric complex, reduced intraluminal pressures (p<0.05-0.01) and increased permeability (p<0.01) through NO-dependent mechanisms. In human intestine, NPS localized at myenteric nerve cell bodies and fibers. NPSR1 was confined to nerve cell bodies. Circulating NPS in humans was tenfold below the ~0.3 nmol/l dissociation constant (Kd) of NPSR1, with no difference between healthy and IBD subjects. In human intestinal muscle strips pre-contracted by bethanechol, NPS 1-1000 nmol/l induced NO-dependent muscle relaxation (p<0.05) that was sensitive also to tetrodotoxin (p<0.01). In conclusion, NPS inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans. Aberrant signaling and up-regulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.
Place, publisher, year, edition, pages
2015. Vol. 309, no 8, G625-G634 p.
inflammation; inflammatory bowel disease; migrating motor complex; NO; peristalsis
IdentifiersURN: urn:nbn:se:uu:diva-264766DOI: 10.1152/ajpgi.00104.2015ISI: 000364068300002PubMedID: 26206857OAI: oai:DiVA.org:uu-264766DiVA: diva2:861477
FunderThe Swedish Medical Association, SLS-176671Swedish Research Council, 7916Swedish Society of Medicine, SLS-176671Swedish National Board of Health and Welfare, SLS-176671
Shared first name: Wan Salman Wan Saudi and Md. Abdul Halim.
Shared last name: Dominic-Luc Webb, Markus Sjöblom and Per M. Hellström.2015-10-162015-10-162016-05-25Bibliographically approved