Effect of Histamine H2-Antagonists on Serum Gastrin Levels in Gastric Lumen-Perfused Rats

The effect of histamine H2-antagonists on serum gastrin concentration and histamine-stimulated gastric acid secretion was studied in gastric lumen-perfused rats in which changes in the intragastric pH were limited by using 2.5 mM propionate-succinate buffer as perfusate. The gastric acid secretion was measured by the titration of the acidity of gastric juice with 0.05 N NaOH. The serum gastrin levels were determined in the blood that was obtained simultaneously with gastric juice by radioimmunoassay. The gastric acid secretion was inhibited by these histamine H2-antagonists--cimetidine, famotidine, ranitidine and TZU-0460 administered intravenously. Within the dose-response range of the inhibition of gastric acid secretion, cimetidine and ranitidine increased significantly the serum gastrin levels, but famotidine and TZU-0460 did not. The doses of famotidine and TZU-0460 which were used to increase the serum gastrin levels were found to be higher than those for the maximal inhibition of gastric acid secretion. They also presented a dose-response curve to the serum gastrin levels similar to cimetidine and ranitidine. The findings suggest that histamine H2-antagonists have a potency to increase serum gastrin levels to that of the inhibition of gastric acid secretion.