Pepsin release by prostaglandin E1 analogue. A potential therapeutic problem
M. D. Basson, K. A. Zucker, T. E. Adrian, M. J. Zdon, G. H. Ballantyne and I. M. Modlin
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.