Modulatory role of 5-HT₃ receptors in gastric function and ethanol-induced mucosal damage in rat stomachs

The involvement of 5-hydroxytryptamine (5-HT) in gastric function and mucosal damage has been defined. 5-HT also potentiates lesion formation in animals. The current study investigated further whether these actions are mediated through 5-HT₃ receptors in rats. Ondansetron, a 5-HT₃ receptor antagonist, was given subcutaneously, 2 or 4 mg/kg, 30 min before the gastric parameters were measured. The higher dose of ondansetron, 4 mg/kg, significantly increased gastric mucosal blood flow (GMBF) and also basal acid and Na⁺ secretion. However, it did not affect pepsin output. 5-HT time dependently reduced GMBF and pepsin secretion, but not that of acid and Na⁺. These actions were not altered by ondansetron pretreatment. The drug, however, dose dependently reduced ethanol-induced gastric mucosal lesions in the 5-HT-treated animals. These findings indicate that 5-HT₃ receptors regulate not only basal GMBF, but also acid and Na⁺ secretion in stomachs. However, the depressive action of 5-HT on GMBF and pepsin secretion is most likely not mediated through 5-HT₃receptors. Ondansetron also modulates the toxicities of ethanol in the stomach and this action is likely to be mediated through the preservation of GMBF.