Effects of H2-Receptor Antagonist on the Cellular Function of Gastric Mucosa in the Rat.

H2-receptor antagonists (H2-blockers) block the H2-receptors on gastric parietal cells and strongly inhibit acid secretion, resulting in an augmented gastrin secretion by gastrin (G) cells. The histamine-producing enterochromaffin-like (ECL) cells contain histidine decarboxylase (HDC), a histamine-forming enzyme, which is controlled mainly by gastrin. HDC has a short biological half-life and sensitive responses and, therefore, is a good marker for ECL cell function. To investigate the mechanisms of action of the H2-receptor antagonists on ECL cells, we examined the changes of gastric mucosal histamine metabolism and gastrointestinal hormones after administration of five H2-blockers. Cimetidine, ranitidine and nizatidine increased both the serum gastrin levels and mucosal HDC activity in a dose-manner. At high doses of famotidine and roxatidine, the gastric pH and serum gastrin levels were increased, but HDC activity was decreased. In addition, famotidine administration lowered the mucosal somatostatin levels and increased serum secretin levels. Famotidine and roxatidine may have acted directly on the ECL cells to lower the sensitivity to gastrin and suppressed HDC activity. The two H2-receptor antagonists, apart from their pharmacological inhibitory effect on ECL cells, may also affect cellular function of gastrin of gastric mucosa by regulating secretion of somatostatin and secretin.