[Effect of tegaserod on the serotonin content in rat ileocaecal mucosa under partial restraint stress].

Objective: To investigate the content and distribution of serotonin in the ileocecal mucosa of rats under partial restraint stress (PRS) and to study the effect of tegaserod on the content of serotonin in the positive cells.

Methods: Male Wistar rats (n = 24) were divided into three test groups. After sham-stress (control group) or PRS had been applied to the rats for two hours, 1-methyl-2-pyrrolidinone (solvent) or tegaserod (a partial 5-HT(4) receptor agonist) was administered intra-peritoneally to the corresponding groups. The cellular distribution and quantitative analysis of 5-HT in the ileocecal mucosa were achieved with immunohistochemical method and computerized image system. The 5-HT content of individual enterochromaffin cells (EC) in tegaserod group and PRS group were observed with immunoelectron microscopic technique.

Results: Serotonin immunoreactivity was mainly found in the epithelium and lamina propria of the mucosa. As compared with the control group, the optical density of serotonin-immunoreactive cells in ileocecal mucosa decreased in the PRS rats (0.326 +/- 0.035 vs 0.362 +/- 0.042, P < 0.001), the optical density of serotonin-immunoreactive cells in ileocecal mucosa in the tegaserod group (0.364 +/- 0.033) was much higher than in the PRS rats (P < 0.001). Immunoelectron microscopic study showed that in the tegaserod group, EC in the epithelium contained more serotonin-positive secretary granules than in the PRS rats.

Conclusions: The increased 5-HT release of positive cells in gut mucosa may be partly responsible for visceral hypersensitivity. The effect of tegaserod on visceral hypersensitivity, at least in part, is likely to act through the pathway involving regulation of gastrointestinal 5-HT release.