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 of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
sulfhydryl SH CNT CNT ethanol hexosamine CNT cinitapride PGE2 SH benzamide 5-HT CNT ethanol PGE2 SH Cinitapride prostaglandins sulfhydryl ethanol 5-hydroxytryptamine CNT 5-HT2 5-HT1 5-HT4 5-HT1 5-HT2 glycoprotein PG 5-HT ethanol 5-hydroxytryptamine 5-HT prostaglandins PGs