Protective Effect of Tegaserod Against Indomethacin-Induced Gastric Injury in the Rat

Gastric contractions induced by non-steroidal anti-inflammatory drugs (NSAIDs) contribute to mucosal ulceration. The goal of the present study was to investigate whether maintaining normal gastric motility provides protection against NSAIDs. A rat model of indomethacin-induced gastric mucosal injury and muscle hypercontratility was used to evaluate the protective effect of pretreatment with the 5-HT4 receptor agonist tegaserod (1 mg/kg b.i.d.) in comparison to the effect of the proton pump inhibitor omeprazole (20 mg/kg b.i.d). Indomethacin induced mucosal ulceration associated with hypercontractility of isolated antral muscle strips in response to KCl, carbachol, 5-HT or electrical field stimulation. Pretreatment with tegaserod alone or in combination with omeprazole prevented both mucosal ulceration and muscle hypercontractility. In contrast, omeprazole protected the mucosa without preventing the development of muscle hypercontractility. The results show that activation of peripheral 5-HT4 receptors promotes normal contractility of the antrum suggesting a different mechanism of gasrtoprotection against NSAIDs.