These results suggest that lafutidine, but not cimetidine, protects the stomach against NH2Cl, whether occurring endogenously or administered exogenously and that this action may be mediated by capsaicin-sensitive sensory neurons.
Abstract-We examined the effects of FPL-52694 and disodium cromoglycate (DSCG), mast cell stabilizers, on HCI ethanol-induced gastric lesions in rats and investigated the factors involved in their protection.Oral (p.o.) administration of 1 ml of HCI ethanol (60% in 150 mM HCI) induced linear hemor hagic lesions in the gastric mucosa within 1 hr. FPL-52694 (1-30 mg/kg), given both p.o. and intraperitoneally (i.p.), prevented these lesions in a dose-related manner. DSCG (3-30 mg/kg) also dose-dependently reduced the formation of these lesions when this agent was given i.p. The protective effects of these drugs on HCI-ethanol induced lesions were significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.).Both gastric acid secretion and transmucosal potential difference were significantly reduced by topical application of FPL-52694 (>10 mg/kg), but were not affected by i.p. administration of FPL-52694 and DSCG. On the other hand, gastric motor activity measured as intraluminal pressure recordings was sig nificantly inhibited for 2 hr by both FPL-52694 (p.o. and i.p.) and DSCG (i.p.), and these effects were also significantly antagonized with prior administration of indomethacin.A significant relationship was found between the effects of these two drugs on the lesion index and the motility index (r: 0.9214, P<0.01), but not other factors.These results suggest that mast cell stabilizers such as FPL-52694 and DSCG protect the gastric mucosa against HCI-ethanol through a systemic action, probably mediated with endogenous prostaglandins. Although the mechanism of cytoprotection remains unknown, this property may be related to their inhibitory effects on gastric motor activity.
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