PROSTAGLANDIN E₂ IN THE RAT GASTRIC MUCOSA (3RD REPORT)

Effect of Cimetidine

Abstract

We induced gastric mucosal lesions in fasting rats with 0.8N HCl and studied the effect of cimetidine on prostaglandin E₂ and cyclic AMP to examine the mechanisms underlying the rebound phenomenon after cimetidine withdrawal.
Prostaglandin levels in the fundic and antral mucosa of control rats were 1.05±0.23 and 2.53±0.44μg/g, respectively; they were significantly lower (0.30±0.08 and 0.41±0.13μg/g, respectively; p<0.01) in cimetidine treated rats (100mg/kg, i. p.). Cyclic AMP levels in the fundic and antral mucosa were also decreased by cimetidine administration.
The ulcer index (total mm length of all ulcer lesions in the fundus and the pyloric antrum) of HCl-treated controls was 42.3±6.7; it was enhanced to 76.3±5.7 by cimetidine. HCl-treated rats received simultaneous administrations of cimetidine and prostaglandin E₂ (100μg/kg, p. o.) did not develop gastric mucosal lesions.
The results suggest that in rats, cimetidine enhances the development of HCl-induced gastric mucosal lesions by reducing intramucosal prostaglandin E₂ and that the rebound phenomenon may occur when the antisecretory effect of cimetidine ceases prior to recovery of the premedication intramucosal prostaglandin E₂ level.