CYTOPROTECTIVE ACTIVITY OF CISAPRIDE ON EXPERIMENTAL GASTRIC-MUCOSAL LESIONS INDUCED BY ETHANOL - ROLE OF ENDOGENOUS PROSTAGLANDINS

The antiulcer effects and protective mechanisms of cisapride, a prokin etic benzamide agonist of 5-HT3 and antagonist of 5-HT4 receptors, wer e investigated in gastric mucosal injury induced by pretreatment with 50% v/v ethanol in rats. The duration of the protective effect was als o studied and the results were compared with those of 5-HT. 240 min af ter administration of cisapride (10, 25 and 50 mg/kg) the total area o f gastric lesions decreased significantly, in macroscopical and histol ogical evaluations, and the mucus, hexosamine, and sulphated glycoprot ein content were significantly increased. Indomethacin partially rever sed cisapride protection suggesting that the beneficial antiulcer effe cts of this drug could be mediated in part by prostaglandins. This stu dy confirms that this benzamide, in this experimental model, enhances gastric PGE(2) production. We also investigated the time course of act ion of 5-HT, 30-240 min before ethanol administration, and our study n or only demonstrates the ulcerogenic action of the amine (30 min of pr etreatment) but also its protective nature, shown macroscopic and micr oscopically, after 240 min of its administration, without any effect o n PGs production. These findings suggest a new gastroprotective featur e of cisapride partly explained through a prostaglandin-dependent mech anism and possibly independent of its 5-HT activity.