The significance of gastrin in the pathogenesis and therapy of peptic ulcer disease

Abstract

Gastrin, a polypeptide hormone secreted by G (gastrin)-cells in the antroduodenal mucosa, is not only a potent stimulant of gastric acid secretion but also exerts trophic actions on the parietal, chief and enterochromaffin-like cells in the oxyntic mucosa. Gastrin plays a crucial role in the pathogenesis of hypergastrinaemic peptic ulcer disease, i.e. in the Zollinger-Ellison syndrome, antral G-cell hyperfunction and retained excluded antrum after subtotal gastrectomy. In patients with normogastrinaemic duodenal ulcer disease the feedback mechanism between gastric acid and gastrin secretion is impaired, while in gastric ulcer patients gastrin secretion is appropriately regulated by gastric acid. Antisecretory drugs may exert varying effects on gastrin secretion. Potent antisecretory drugs, such as omeprazole, increase serum and antral gastrin concentrations, whereas histamine H2-receptor antagonists, such as cimetidine, ranitidine, famotidine and roxatidine, have little influence on gastrin. Interestingly, antisecretory doses of prostaglandin E2-analogues, such as enprostil and arbaprostil [15(R)-15-methylprostaglandin E2], inhibit gastrin secretion, while gastrin is not influenced by prostaglandin E1-analogues, e.g. misoprostol. Somatostatin and the somatostatin-analogue SMS 201-995 reduce serum gastrin levels and gastric acid secretion.