Prostaglandin E Inhibits Indomethacin-Induced Gastric Lesions through EP-1 Receptors
Backgrounds and Aims: We examined the effect of various prostaglandin E (PGE) analogs specific to EP receptor subtypes on indomethacin-induced gastric lesions in rats and investigated which EP receptor subtype is involved in the protective action of PGE 2 using EP-receptor knockout mice. Methods: Ga...
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Published in | Digestion Vol. 63; no. 2; pp. 92 - 101 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
Karger
01.01.2001
S. Karger AG |
Subjects | |
Online Access | Get full text |
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Summary: | Backgrounds and Aims: We examined the effect of various prostaglandin E (PGE) analogs specific to EP receptor subtypes on indomethacin-induced gastric lesions in rats and investigated which EP receptor subtype is involved in the protective action of PGE 2 using EP-receptor knockout mice. Methods: Gastric lesions were induced by subcutaneous administration of indomethacin (35 mg/kg). Gastric motility was measured using a balloon method, while neutrophil chemotaxis determined using a Boyden chamber. Results: Indomethacin-induced gastric lesions were significantly prevented by PGE 2 as well as atropine, and the former effect was mimicked by sulprostone (EP 1 /EP 3 ) and 17-phenyl PGE 2 (EP 1 ) and antagonized by an EP 1 antagonist, ONO-AE-829. Neither butaprost (EP 2 ), ONO-NT-012 (EP 3 ) nor 11-deoxy PGE 1 (EP 3 /EP 4 ) showed any protection on the lesions. Indomethacin caused a marked increase in gastric motility; the response preceded the onset of lesions and was inhibited by atropine as well as PGE derivatives acting as EP 1 receptors. Neutrophil chemotaxis was inhibited by PGE 2 , butaprost and slightly by 11-deoxy PGE 1 , but not by either 17-phenyl PGE 2 , ONO-NT-012 or atropine. In addition, indomethacin caused damage similarly in both wild-type and knockout mice lacking EP 1 or EP 3 receptors, yet the protective action of PGE 2 was observed in wild-type and EP 3 receptor knockout mice but totally disappeared in mice lacking EP 1 receptors. Conclusion: PGE 2 inhibits indomethacin-induced gastric lesions, through EP 1 receptors, and this effect may be functionally associated with inhibition of gastric motility but not of neutrophil activation/migration. |
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ISSN: | 0012-2823 1421-9867 |
DOI: | 10.1159/000051876 |