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Arch Surg. 1988 Apr;123(4):431-3.

Pepsin release by prostaglandin E1 analogue. A potential therapeutic problem.

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Department of Surgery, Yale University School of Medicine, New Haven, Conn.


Prostaglandins Inhibit gastric acid secretion and are independently "cytoprotective" for gastric mucosa. They are currently under clinical Investigation for the treatment of peptic ulcers. The effects of the prostaglandin E1 analogue misoprostol on pepsinogen and acid secretion were tested in isolated rabbit gastric glands and enriched parietal cells. Pepsinogen concentrations were measured by iodine 125-labeled albumin digestion and acid secretion indirectly by carbon 14-tagged aminopyrine uptake. Misoprostol inhibited histamine-stimulated acid secretion in parietal cells with 50% inhibition at 10(-9) mol/L and maximally (78% inhibition) at 10(-7) mol/L. In contrast, however, misoprostol strongly stimulated pepsinogen secretion by gastric glands with a half-maximal effect at 10(-8) mol/L and maximal stimulation of 227% at 10(-6) mol/L. It is possible that this release of pepsin could compromise the action of prostaglandins in promoting ulcer healing.

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