CINITAPRIDE PROTECTS AGAINST ETHANOL-INDUCED GASTRIC-MUCOSAL INJURY IN RATS - ROLE OF 5-HYDROXYTRYPTAMINE, PROSTAGLANDINS AND SULFHYDRYL COMPOUNDS

This study was designed to determine the gastroprotective properties o f cinitapride (CNT), a novel prokinetic benzamide derivative agonist o f 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury pr oduced by 50% (v/v) ethanol. Results were compared with those for 5-hy droxytryptamine (5-HT: 10 mg kg(-1)). The possible involvements of gas tric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl c ompounds (SH) in the protection mediated by CNT were also examined. In traperitoneal administration of CNT (0.50 and 1 mg kg(-1)), 30 min bef ore ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg(-1)) also produc ed a significant increase in gastric mucosal levels of PGE(2), but did not induce any significant changes in SH values. On the contrary, pre treatment with 5-HT worsened ethanol-induced erosions, however, did no t affect gastric mucus secretion, glycoprotein content or PGE(2) level s, although the non-protein SH fraction was significantly decreased. T he present results demonstrate that the gastroprotective effects of CN T could be partly explained by a complex PG dependent mechanism. We su ggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade a nd 5-HT1 receptor activation could be also involved.