FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats

American Journal of Physiology. Gastrointestinal and Liver Physiology
Yasutada AkibaJonathan D Kaunitz

Abstract

Serotonin (5-HT), predominantly synthesized and released by enterochromaffin cells, is implicated in gastrointestinal symptoms such as emesis, abdominal pain, and diarrhea. Because luminal short-chain fatty acids (SCFAs) release 5-HT from enterochromaffin cells, which express the SCFA receptor free fatty acid receptor 2 (FFA2) in rat duodenum, we examined the effects of the selective FFA2 agonist phenylacetamide-1 (PA1) on duodenal 5-HT release with consequent bicarbonate secretion [duodenal bicarbonate secretion (DBS)] and on indomethacin (IND)-induced enteropathy. Intestinal injury was induced by IND (10 mg/kg sc) with or without PA1. We measured DBS in vivo in a duodenal loop perfused with PA1 while measuring 5-HT released in the portal vein. Duodenal blood flow was measured by laser-Doppler flowmetry. IND induced small intestinal ulcers with duodenal sparing. PA1 given with IND (IND + PA1) dose dependently induced duodenal erosions. IND + PA1-induced duodenal lesions were inhibited by the FFA2 antagonist GLPG-0974, ondansetron, or omeprazole but not by RS-23597 or atropine. Luminal perfusion of PA1 augmented DBS accompanied by increased portal blood 5-HT concentrations with approximately eight times more release at 0.1 mM t...Continue Reading

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Citations

Jul 11, 2019·Current Gastroenterology Reports·Mari IwasakiJonathan D Kaunitz
Aug 21, 2018·Current Opinion in Gastroenterology·Mari IwasakiJonathan D Kaunitz
Aug 15, 2017·Current Opinion in Gastroenterology·Izumi Kaji, Jonathan D Kaunitz
Jan 27, 2021·Trends in Pharmacological Sciences·Graeme MilliganAndrew B Tobin

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BETA
ELISA
biopsy

Software Mentioned

GraphPad Prism

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