ANTISECRETORY EFFECT OF DS-4574, A MAST-CELL STABILIZER WITH PEPTIDOLEUKOTRIENE ANTAGONISM, ON GASTRIC-ACID SECRETION

The antisecretory effect of DS-4574, a mast cell stabilizer with pepti doleukotriene antagonism, on the hypersecretion of gastric acid stimul ated by several secretagogues was examined in the pig. Goettingen mini ature pigs with chronic gastric fistula were used. Intramuscular injec tion of carbachol (60 mu g/kg), tetragastrin (50 mu g/kg) or histamine (200 mu g/kg)-induced gastric acid hypersecretion. Intraduodenal admi nistration of DS-4574 (10 and 20 mg/kg) significantly inhibited both t he hypersecretion induced by carbachol and that by tetragastrin. On th e other hand, DS-4574 (50 mg/kg, intraduodenal) did not suppress hista mine-induced hypersecretion. In the in vitro study, no effect on hog g astric K+-dependent ATPase activity was found at concentrations of DS- 4574 from 10(-7) to 10(-4) M. These results were highly similar to tho se in the rat. The suppression of histamine release from histamine-con taining cells in the gastric mucosa of the rat was concluded to be an antisecretory effect of DS-4574.