Mucosal 5‐HT4 Receptors: A Novel Therapeutic Target in Colitis

• DOI: 10.1096/fasebj.29.1_supplement.854.6
• Publication Date: 2021-06-21T17:05:54Z
• Authors: Stephanie Spohn; Brigitte Lavoie; Sarah MacEachern; Jane Roberts; Rebecca Wilcox; Keith Sharkey; Gary Mawe
• Keywords: Tegaserod; 5-HT4 receptor; Enterochromaffin cell

We have previously shown that 5-HT4 receptors are expressed in colonic epithelium, and agonists produce physiological responses such as mucus secretion from goblet cells, chloride enterocytes, serotonin release enterochromaffin cells. These may protective actions the colon conditions like colitis. To test this hypothesis, we induced colitis CD-1 mice using 4% DSS (w/v) drinking water or a single enema of TNBS (7.5mg/mL 50% ethanol) treated with receptor agonist, Tegaserod (1mg/kg), plus antagonist, GR113808, vehicle. Animals were during (days 1-7) following 7-15) development effect treatment on propulsive motility, guinea pigs administered days 1-7, distal motility was evaluated. Inflammation evaluated by Disease Activity Index (DAI), Macroscopic Damage Scores (MDS), histological damage scores. found reduced severity 7d model compared to vehicle inflamed animals measured DAI (p<0.05), MDS (p<0.01) H&E scores (p<0.001), able block these effects GR113808. In 15d paradigm, recovery accelerated. Also, dysmotility significantly reversed agonist treatment. Taken together, data suggest activation mucosal reduces of, speeds from, inflammation. Funded DK62267