Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers.
Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue of prostaglandin E1, influences gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes). Nine healthy volunteers were studied in a single blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4. These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a changed profile, of native eicosanoids modulating the release of inflammatory mediators from immune cells might explain why prostaglandin analogues have a comparatively poor clinical performance in ulcer healing and prevention.
Mertz-Nielsen
A
A
Department of Medical Gastroenterology, Hvidovre Hospital, Denmark.
Eskerod
O
O
Bukhave
K
K
Rask-Madsen
J
J
D000328:Adult; D018592:Cross-Over Studies; D003864:Depression, Chemical; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000494:pharmacology*; D016037:Single-Blind Method; D013929:Thromboxane B2 / Q000378:metabolism*
D016595:Misoprostol; D007975:Leukotriene B4; D013929:Thromboxane B2; D015232:Dinoprostone