The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse

Abstract

BackgroundEnteric serotonin may function as a mucosal growth factor. Previous work demonstrated increased crypt cell proliferation and intestinal mucosal surface area with potentiation of serotonin. While an indirect mechanism was postulated to explain these effects, the presence of 5-HT4 receptors on enterocytes raises the possibility of a direct action of serotonin. We hypothesized that a 5-HT4 specific agonist, prucalopride, would stimulate intestinal mucosal growth and enhance absorptive function in the murine small intestine. MethodsAdult wild-type mice were treated parenterally with prucalopride for 14 days via surgically implanted osmotic pumps. In vivo d-xylose absorption was assessed by oral gavage and serum d-xylose measurements. On day 14, glucose absorption was assessed by instilling a glucose solution into isolated segments of small intestine. The bowel was harvested and examined for morphologic parameters and crypt cell proliferation. ResultsVillus height, crypt depth, and crypt proliferation were significantly increased in the distal small bowel of prucalopride-treated mice compared with control animals. Crypt depth was also increased in the proximal and middle small intestine in treated mice. There was no difference in d-xylose absorption throughout the study period; however, glucose absorption was significantly increased in the distal small intestine of prucalopride-treated mice. ConclusionParenteral administration of the 5-HT4 receptor specific agonist, prucalopride, results in morphologic and functional changes in the murine small intestine that are most prominent in the distal small bowel. While further studies are necessary to delineate the mechanism, it is plausible that the effects are mediated by 5-HT4 receptors on enterocytes.