Effects of misoprostol, (±)-methyl (11α, 13E)-11, 16-dihydroxy-16-methyl-9-oxoprost-13-en-1-oate, on various gastric and duodenal lesions in rats

Male Sprague-Dawley rats (230 ?? 280 g), either fasted for 15-24 hr or non-fasted prior to experiments, were used. Misoprostol (3 ?? 100 μg/kg, p.o.) dose-dependently inhibited the development of 150 mM HCl·aspirin (100 mg/kg)-, 150 mM HCl·60% ethanol-, and aspirin (150 mg/kg)-induced gastric lesion...

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Veröffentlicht in:Folia Pharmacologica Japonica 1986, Vol.87(3), pp.339-350
Hauptverfasser: OKABE, Susumu, TAKEUCHI, Koji, UEKI, Shigeru, INOUE, Yayoi, SUNAMOTO, Mie
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Sprache:jpn
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Zusammenfassung:Male Sprague-Dawley rats (230 ?? 280 g), either fasted for 15-24 hr or non-fasted prior to experiments, were used. Misoprostol (3 ?? 100 μg/kg, p.o.) dose-dependently inhibited the development of 150 mM HCl·aspirin (100 mg/kg)-, 150 mM HCl·60% ethanol-, and aspirin (150 mg/kg)-induced gastric lesions. Misoprostol (30, 100 μg/kg, p.o.), given twice daily for 4 days, significantly inhibited prednisolone (50 mg/kg given once daily for 4 days)-induced gastric lesions. Misoprostol (30 or 2×300 μg/kg, p.o.) also significantly inhibited water-immersion stress (21°C, 10 hr)-induced gastric lesions or mepirizole (200 mg/kg)-induced duodenal lesions, respectively. In contrast, misoprostol (30 ?? 300 μg/kg, p.o.) hadno effects on indomethacin (25 mg/kg)- and mepirizole (200 mg/kg)-induced gastric lesions. Misoprostol (30 μg/kg, p.o.) had no effect on gastric secretion in pylorus-ligated preparations (4 hr), but it (100 or 300 μg/kg, p.o.) significantly increased the volume and pepsin output. Gastric motility, either normal or enhanced with indomethacin (25 mg/kg), was inhibited by misoprostol (30 or 300 μg/kg, p.o.). Misoprostol (30 μg/kg, i.d.) significantly stimulated duodenal HCO3- secretion. Mechanisms by which misoprostol inhibits various gastric lesions remain unknown. However, the stimulatory activity on duodenal HCO3- secretion appears to be involved in the preventive effect of misoprostol on the development of duodenal lesions. The effects of cimetidine and 16, 16-dimethyl PGE2 were also studied and compared with those of misoprostol.
ISSN:0015-5691
1347-8397
DOI:10.1254/fpj.87.339