Ethacrynic acid and sulphasalazine inhibit the generation of leukotriene C4 in rat stomachs: a possible gastric anti-ulcer mechanism in cold-restraint-stressed rats.
The role of gastric glandular mucosal leukotriene C4 in gastric ulceration, produced by restraint at 4 degrees C (stress) for 2 h in rats, was studied in relation to the ulcer-preventing effects of ethacrynic acid, sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), AA-861 and ONO-1078. Stress itself significantly raised mucosal leukotriene C4 levels; pretreatment with ethacrynic acid, sulphasalazine, sulphapyridine or AA-861 antagonised these changes and reduced the severity of gastric ulceration. Mucosal mast cell degranulation was prevented by ethacrynic acid, sulphasalazine, 5-aminosalicylic acid, AA-861 or ONO-1078; the mucus-depleting effect of stress was also reversed by all these drugs, except for 5-aminosalicylic acid. The anti-ulcer effect of ethacrynic acid and sulphasalazine appears to be related to their influence on glandular mucosal leukotriene C4 levels.
Garg
G P
GP
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Cho
C H
CH
Ogle
C W
CW
D000818:Animals; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D005752:Gastric Mucins / Q000032:analysis; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000378:metabolism*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology; D013312:Stress, Physiological / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology*
D005752:Gastric Mucins; D013189:SRS-A; D012460:Sulfasalazine; D004976:Ethacrynic Acid