Effects of Ecabet Sodium (TA-2711), a New Antiulcer Agent, on Gastrointestinal Mucosal Prostanoid Production and Morphology in Rats

抄録

Effects of ecabet sodium (TA-2711), a locally acting antiulcer agent, on prostanoid production and the morphology of the rat gastrointestinal mucosa were studied in comparison with sucralfate. Ecabet, at therapeutic doses (25 and 100 mg/kg, p.o.), dose-dependently increased the gastric mucosal level of prostaglandin E₂ (PGE₂) : sucralfate (100 mg/kg, p.o.) showed a tendency to increase the PGE₂ level. In an ex vivo study, ecabet (25 and 100 mg/kg, p.o.) dose-dependently increased the capacity of the gastric mucosa to synthesize PGE₂ and PGI₂ without modifying tromboxane A₂ (TXA₂) synthesis, and the 100 mg/kg dose persisted for up to 3 h. Ecabet (400 mg/kg, p.o.) also significantly increased PGE₂ synthesis and there was a tendency to increase PGI₂ synthesis by the duodenal mucosa, without affecting TXA₂ synthesis. PGE₂ synthesis by the colonic mucosa was not affected, even at a high dose of ecabet (1000 mg/kg, p.o.). When the rat gastric mucosa was examined by light microscopy and scanning electron microscopy, ecabet (100 and 400 mg/kg, p.o.) had caused no morphological change to the gastric mucosa, while sucralfate (100 and 400 mg/kg, p.o.) produced apical rupture of the epithelial cells and subepithelial edema. The present study indicates that ecabet locally stimulates PGE₂ and PGI₂ production in the gastroduodenal mucosa and this effect is not attributable to a local irritant action accompanied by superficial epithelium damage.