Effects of Omeprazole and Ranitidine on Gastric Acid Secretion, Blood Gastrin Levels and [3H]-Thymidine Incorporation in the Oxyntic Mucosa from Dogs and RatsRyberg B. · Mattsson H. · Carlsson E.
Gastrointestinal Research, Department of Biology, AB Hässle, Mölndal, Sweden
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Dogs provided with a gastric fistula were treated orally for 1 week either with the H+, K+-ATPase inhibitor omeprazole, 80 μmol/kg once daily, or with the histamine H2 receptor antagonist ranitidine, 85–175 μmol/kg every 8 h. Acid secretion, serum gastrin levels and [3H]-thymidine incorporation in the corpus mucosa were determined before, during and after the treatment period. In order to examine differences between species, plasma gastrin levels and [3H]-thymidine incorporation in the oxyntic mucosa were also determined in female rats treated up to 1 week with omeprazole, 400 μmol/kg orally once daily. Histamine-stimulated gastric acid secretion in dogs treated with omeprazole or ranitidine was almost completely inhibited during the whole treatment period. As a consequence of that, the meal-stimulated gastrin levels were increased (7-fold) during treatment by both compounds. [3H]-thymidine incorporation in the dog corpus mucosa was increased approximately 4 times on day 5 both with omeprazole and ranitidine. After the treatment was stopped, gastric acid secretion, serum levels of gastrin and the rate of [3H]-thymidine incorporation were back to control level in both groups within 11 days. In the rats, the plasma gastrin levels increased 10-fold and the rate of [3H]-thymidine incorporation in the corpus mucosa increased 3-fold during treatment with omeprazole. In conclusion, a pronounced suppression of gastric acid secretion over the day with antisecretagogues results in hypergastrinemia in both dogs and rats. As a consequence of the trophic effect of gastrin, the incorporation of [3H]-thymidine in the oxyntic mucosa is increased. The results show that these effects are obtained regardless of the mechanism by which acid secretion is inhibited.
© 1988 S. Karger AG, Basel
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