Effect of dexamethasone on the peptic activity of gastric lumen and mucosa

Abstract

Dexamethasone (9α-nuoro-16α methyl-11β ,17α, 21-trihydroxy-1,4-pregnadiene-3, 20-dione-21-phosphate), a synthetic glucocorticoid, has a dual role on pepsinogen content of the gastric lumen and mucosa as measured by its peptic activity. Following stimulation the luminal peptic activity gradually decreases after 6 hr, then returns to basal levels at 18 hr and by 24 hr is inhibited by 50%. The luminal peptic activity induced by the secretory compound mercaptomethylimidazole (MMI) is also decreased. Dexamethasone effect on both basal and MMI-induced peptic activity can be reproduced by cycloheximide or puromycin, translational blockers of protein synthesis. This drug also has an independent time and dose-dependent inhibitory effect on gastric mucosal peptic activity which does not correlate with increased peptic activity of the lumen. Dexamethasone appears to be more effective than hydrocortisone and corticosterone in inhibiting the basal peptic activity of both lumen and mucosa. The inhibitory effect of this drug on tissue peptic activity is not mediated through induction of any inhibitory protein as evidenced by the insensitivity of the effect to actinomycin D. Studies on [¹⁴C]phenylalanine incorporation into gastric protein indicate that the effect of dexamethasone on tissue pepsinogen content is not due to a generalized block of protein synthesis.