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  • 1
    ISSN: 1420-908X
    Keywords: DS-4574 ; Mast cell stabilizer ; Gastric acid secretion ; Carbachol ; Tetragastrin ; Histamine ; Goettingen miniature pigs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 thein vitro study, no effect on hog gastric K+-dependent ATPase activity was found at concentrations of DS-4574 from 10−7 to 10−4 M. 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Keywords: DS-4574 ; Mast cell stabilizer ; Compound 48/80 ; Gastric mucosal lesions ; Disodium cromoglycate ; LY171883 ; Cimetidine ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on rat gastric mucosal lesions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H2 receptor antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly inhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia and histamine release from rat peritoneal mast cells induced by C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidoleukotriene antagonistic activity.
    Type of Medium: Electronic Resource
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