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Gastric Motility and Mucosal Ulcerogenic Responses Induced by Rats Under Prostaglandin-Deficient Conditions Prokinetic Drugs in

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Abstract

The present study was performed to examinewhether gastric prokinetic drugs may induce damage inthe rat stomach under normal and prostaglandin(PG)-deficient conditions. Male SD rats fasted for 18 hrwere administered subcutaneously with threedifferent prokinetic drugs such as metoclopramide (3-60mg/kg), ondansetron (0.3-3 mg/kg), and cisapride (3-30mg/kg). Half the number of these animals were pretreated with indomethacin (5 mg/kg) subcutaneously forinduction of PG deficiency in the stomach.Administration of these drugs increased gastric motoractivity in a dose-dependent manner and expeditedgastric emptying at lower doses than those affectinggastric motility; the potency of the hypermotilityeffect was in the following order: metoclopramide =ondansetron > cisapride. None of these drugs alonecaused gross damage in the stomach, although whitishrough areas were observed in the gastric mucosa alongthe folds. In the rats pretreated with indomethacin,however, both metoclopramide and ondansetron provoked multiple hemorrhagic lesions in the gastricmucosa. Indomethacin at this dose showed over 90%inhibition of cyclooxygenase activity without causingany damage in the stomach, and this PG-deficient effect was not affected by coadministration with theprokinetic drugs. The mucosal ulcerogenic responsesinduced by metoclopramide in the presence ofindomethacin were significantly inhibited by prioradministration of atropine (1 mg/kg) or PGE2 (300μg/kg) at doses that inhibited gastric hypermotilityinduced by metoclopramide. These results suggest that:(1) gastric prokinetic drugs induce damage in ratstomachs under PG-deficient conditions at the doses that enhance gastric motility and emptying but notat the doses that expedite gastric emptying only, and(2) gastric hypermotility has the potential to causegross damage in the stomach, supporting the importance of gastric motility as a pathogenic element ofgastric lesions.

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Authors
  1. Koji Takeuchi
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  2. Shinichi Kato
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  3. Takuya Hirata
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  4. Hidekazu Nishiwaki
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Takeuchi, K., Kato, S., Hirata, T. et al. Gastric Motility and Mucosal Ulcerogenic Responses Induced by Rats Under Prostaglandin-Deficient Conditions Prokinetic Drugs in. Dig Dis Sci 42, 251–258 (1997). https://doi.org/10.1023/A:1018889129410

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