Gastric protection by sucralfate. Role of mucus and prostaglandins.
Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.
Shea-Donohue
T
T
Steel
L
L
Montcalm
E
E
Dubois
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000502:physiology; D000535:Aluminum / Q000627:therapeutic use*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001241:Aspirin; D015237:Dinoprost; D015232:Dinoprostone; D008253:Macaca mulatta; D009093:Mucus / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000502:physiology; D011460:Prostaglandins F / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013392:Sucralfate
D000897:Anti-Ulcer Agents; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013392:Sucralfate; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D000535:Aluminum; D015232:Dinoprostone; D001241:Aspirin