Role of endogenous gastric prostanoids in the pathogenesis and therapy of duodenal ulcer.
Synthesis of prostaglandin E2 and 6-keto prostaglandin F1 alpha by cultured antral and fundic gastric mucosa obtained from 86 patients with active duodenal ulcer who were not receiving medication was 50% lower (p less than 0.01) than their respective synthesis by cultured gastric mucosa in normal subjects. Antral and fundic prostanoid synthesis in patients receiving chronic therapy with nonsteroidal antiinflammatory drugs was almost completely inhibited. The decreased synthesis of antral and fundic prostaglandin E2 and 6-keto prostaglandin F1 alpha in duodenal ulcer patients was not affected following ulcer healing achieved after 4 wk of therapy with placebo, arbacet, misoprostol, sucralfate, and pirenzepine. In contrast, following 4 wk of therapy with ranitidine, both antral and fundic prostaglandin E2 synthesis were significantly increased when compared with their respective synthesis before therapy. These results confirm that gastric prostanoid synthesis is decreased in patients with active duodenal ulcer and in subjects treated with nonsteroidal antiinflammatory drugs, suggesting that decreased endogenous prostanoid synthesis may contribute to the pathogenesis of mucosal damage. The induction of endogenous prostanoids by ranitidine may contribute to its therapeutic effect.
Rachmilewitz
D
D
Ligumsky
M
M
Fich
A
A
Goldin
E
E
Eliakim
A
A
Karmeli
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000535:Aluminum / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001570:Benzodiazepinones / Q000627:therapeutic use; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016595:Misoprostol; D010890:Pirenzepine; D011458:Prostaglandins E / Q000378:metabolism* / Q000627:therapeutic use; D011706:Pyloric Antrum / Q000378:metabolism*; D011899:Ranitidine / Q000627:therapeutic use; D013392:Sucralfate
D000893:Anti-Inflammatory Agents; D001570:Benzodiazepinones; D011458:Prostaglandins E; D016595:Misoprostol; D010890:Pirenzepine; D013392:Sucralfate; D015121:6-Ketoprostaglandin F1 alpha; D011899:Ranitidine; D000535:Aluminum; D000527:Alprostadil