Antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on gastric acid secretion in the pig

The antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on the hypersecretion of gastric acid stimulated by several secretagogues was examined in the pig. Goettingen miniature pigs with chronic gastric fistula were used. Intramuscular injection of carbachol (60 μg/kg), tetragastrin (50 μg/kg) or histamine (200 μg/kg)-induced gastric acid hypersecretion. Intraduodenal administration of DS-4574 (10 and 20 mg/kg) significantly inhibited both the hypersecretion induced by carbachol and that by tetragastrin. On the other hand, DS-4574 (50 mg/kg, intraduodenal) did not suppress histamine-induced hypersecretion. In the in vitro study, no effect on hog gastric K⁺-dependent ATPase activity was found at concentrations of DS-4574 from 10^-7 to 10^-4M. These results were highly similar to those in the rat. The suppression of histamine release from histamine-containing cells in the gastric mucosa of the rat was concluded to be an antisecretory effect of DS-4574.