THE EFFECTS OF OMEPRAZOLE AND FAMOTIDINE ON MUCIN AND PGE(2) RELEASE IN THE RAT STOMACH

Background: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interf ere with mucosal protection and limit the efficacy of the agents. Meth ods: Rats were dosed with famotidine, omeprazole, or buffer control fo r 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate c omposition and prostaglandin E(2) (PGE(2)) release were measured durin g and after drug treatment. Results: PGE(2) release was maximally inhi bited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glyc oprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE(2) release and s ulphated glycoprotein synthesis were restored to control values or mor e by the 5th day after the end of dosing, at which time total glycopro tein synthesis was significantly suppressed in both groups. Histologic ally, a reduction of PAS-positive surface mucus was observed after 2 w eeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment. Conclusions: These results suggest that long-term antisecretory therapy also affects the production of factors involved in primary gastric mucosal defence, wh ich should be considered in the assessment of response to treatment in clinical trials.