MISOPROSTOL INHIBITS GASTRIC-MUCOSAL RELEASE OF ENDOGENOUS PROSTAGLANDIN E(2) AND THROMBOXANE B-2 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 inhi bit gastric acid secretion and they are less effective than histamine H-2 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 mu g) of misoprostol, a synthetic analogue of prostaglandin E(1), influences g astric mucosal release of endogenous prostaglandin E(2) (PGE(2)), thro mboxane B-2 (TXB(2)), and chemotactic leukotriene B-4 (LTB(4)) 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 significantl y decreased basal as well as acid stimulated output of PGE, and TXB(2) , without affecting output of LTB(4). These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentr ations, or even a changed profile, of native eicosanoids modulating th e release of inflammatory mediators from immune cells might explain wh y prostaglandin analogues have a comparatively poor clinical performan ce in ulcer healing and prevention.