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.
Alarcón-de-la-Lastra Romero
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Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Sevilla, España.
López
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Martín
M J
MJ
la Casa
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Motilva
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D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D011453:Prostaglandins / Q000032:analysis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000502:physiology*
D001549:Benzamides; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D012701:Serotonin; D000431:Ethanol; C045316:cinitapride