Papers

2 2010

The 5-HT4 receptor agonist mosapride attenuates NSAID-induced gastric mucosal damage

JOURNAL OF GASTROENTEROLOGY
  • Masahiko Fujisawa
  • ,
  • Takahisa Murata
  • ,
  • Masatoshi Hori
  • ,
  • Hiroshi Ozaki

Volume
45
Number
2
First page
179
Last page
186
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1007/s00535-009-0170-3
Publisher
SPRINGER TOKYO

The cholinergic anti-inflammatory pathway is a novel physiological mechanism found at various locations in the body where the nicotinic regulation of inflammatory cells through the autonomic nervous system is involved. In this study, we tested the hypothesis that cholinergic nerve stimulation by a 5-HT4 agonist may modulate the progression of gastric mucosal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs).
Acute gastric ulcers were induced in rats by the oral administration of indomethacin.
Gastric damage analysis indicated that pretreatment with mosapride, a selective 5-HT4 agonist, at 0.25, 0.5, and 0.75 mg/kg, inhibited the mucosal damage induced by indomethacin. In gastric emptying analysis, an evacuation effect was observed in the 3.0 mg/kg mosapride pretreatment group, but this effect was not observed in the lower dose (0.5 mg/kg) group. The antiulcerogenic activity of mosapride treatment (at 0.5 mg/kg) was blocked by a 5-HT4-specific antagonist, GR113808 (1 mg/kg, i.v.). Additionally, we demonstrated that methyllycaconitine (0.29 and 0.87 mg/kg i.p.), a selective inhibitor of alpha 7 nicotinic acetylcholine (ACh) receptors (alpha 7nAChRs), ablated the antiulcerogenic action of mosapride.
These results suggest that the mucosal protective action of mosapride may be mediated by an action on immune cells through the acceleration of ACh release from parasympathetic nerves via the activation of 5-HT4 receptors, followed by activation of the nicotinic anti-inflammatory system. It appears that the alpha 7nAChR may be involved in the antiulcerogenic action of mosapride.

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Link information
DOI
https://doi.org/10.1007/s00535-009-0170-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20012106
Scopus
https://www.scopus.com/record/display.uri?eid=2-s2.0-77949262990&origin=inward
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000274521100006&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77949262990&origin=inward

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