Antiulcer drugs and gastric prostaglandin E2: an in vitro study.
Prostaglandin (PG) has been reported to be an important protective and acid-suppressive factor in the gastric mucosa. Although the mechanisms of some antiulcer drugs are attributed to their stimulatory effects on endogenous prostaglandins, an understanding of these actions has not been established. In the present study we investigated the effects of antiulcer drugs on PGE2 using cultured gastric mucosal cells. Rabbit gastric mucosal cells were cultured after isolation with collagenase and ethylenediaminetetraacetic acid. PGE2 was measured by enzyme-linked immunoassay. Histamine H2-blockers (cimetidine, ranitidine, famotidine), omeprazole, and sucralfate did not modulate the media content of PGE2, whereas sofalcone dose- and time-dependently increased it. Sofalcone-induced increase of PGE2 was dose-dependently prevented by indomethacin. Sofalcone did not affect intracellular Ca2+ as assessed by the calcium-sensitive probe indo-1. Deprivation of Ca2+ in the media did not modulate the action of sofalcone. Sofalcone significantly suppressed 15-OH-PG dehydrogenase. These results suggest that among the various antiulcer drugs only sofalcone increases PGE2, which may be a factor in its therapeutic effect against peptic ulcer diseases.
Ota
S
S
Department of Internal Medicine 2, Faculty of Medicine, University of Tokyo, Japan.
Takahashi
M
M
Yoshiura
K
K
Hata
Y
Y
Kawabe
T
T
Terano
A
A
Omata
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D011817:Rabbits; D013392:Sucralfate / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D047188:Chalcones; D006635:Histamine H2 Antagonists; C035032:sofalcone; D013392:Sucralfate; D002599:Chalcone; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone; D009853:Omeprazole; D002118:Calcium