Effects of Omeprazole and Ranitidine on Gastric Acid Secretion, Blood Gastrin Levels and [³H]-Thymidine Incorporation in the Oxyntic Mucosa from Dogs and Rats

Abstract

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.

Influence of pineal indoleamines on the mitotic activity of gastric and colonic mucosa epithelial cells in the rat: Interaction with omeprazole

“…The stimulatory effect of OM seems to depend on endogenous gastric hypersecretion; in our study, gastrin levels were markedly elevated in OM-treated rats. This observation is in agreement with the earlier data of other authors [Hakanson et al, 1986;Ryberg et al, 1988;Sundler et al, 19861. Surprisingly, in the present study OM has failed to stimulate cell proliferation of the gastric epithelium, what is in apparent contrast with the previous report on the increase of [3H]-thymidine incorporation into DNA of oxyntic mucosa cells in rats and dogs, following one-week OM administration [Ryberg et al, 19881.…”

“…Considering that gastrin is a well-known stimulator of the gut motility [Grossman, 19731, the actions of Me1 and gastrin appear to ' It: in an apparent contrast to each other. It also ;ems fairly probable that Me1 and gastrin exert opposite effects on intracellular CAMP content in the digestive tract [Ochiai et al, 1985;Altomonte et al, 1986;Lewinski et al, 19891. Omeprazole (OM), a benzimidazole derivative and well-known inhibitor of H+ ,K+-ATPase, was repeatedly shown to inhibit gastric acid secretion in different species, thus leading to hypergastrinaemia and, subsequently, to the trophic effects in the digestive tract [Sundler et al, 1986;Ryberg et al, 1988;Tielemans et al, 19891. In other words, OM has an indirect stimulatory effect on cell proliferation, by elevating the endogenous gastrin levels.…”

Normal Dogs Treated with Famotidine for 14 days Have Only Transient Increases in Serum Gastrin Concentrations

“…In a study of dogs treated with ranitidine for 7 days, basal serum gastrin concentrations peaked at day 4 after starting treatment, comparable to our results, and remained increased through day 7. 26 In this study, fasting gastrin concentrations had returned to baseline 8 days after ranitidine was stopped, but there were no measurements of serum gastrin concentrations between days 7 and 15 so the time at which dogs returned to baseline could not be determined. Results of studies in humans of the effect of H2RAs on serum gastrin concentrations have been comparable to, or different from, our results.…”

“…As hypothesized, mean serum gastrin concentrations peaked by day 3 of famotidine administration, but instead of remaining above basal concentrations, serum gastrin concentration had returned to baseline by day 14, the last day of famotidine administration, in all dogs. In a study of dogs treated with ranitidine for 7 days, basal serum gastrin concentrations peaked at day 4 after starting treatment, comparable to our results, and remained increased through day 7 . In this study, fasting gastrin concentrations had returned to baseline 8 days after ranitidine was stopped, but there were no measurements of serum gastrin concentrations between days 7 and 15 so the time at which dogs returned to baseline could not be determined.…”

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

“…163) With prolonged treatment in rats, such drugs invariably result in marked hypergastrinemia due to sustained inhibition of gastric acid secretion. [164][165][166][167][168][169][170][171][172][173] It is well known that gastrin has a trophic effect on gastrointestinal mucosal cells, to include surface epithelial and ECL cells. In recent years, the underlying mechanism of gastrin's trophic effect has been elucidated at the molecular level.…”