The purpose of this review, based upon 40 years of research, is to clear old controversies. The gastric juice is a strong
acid with active
enzymes (
pepsin and
lipase); ideal for killing swallowed microorganisms. Totally isolated rat stomach and
histamine determination. Human gastric
carcinomas were examined for ECL cell differentiation because tumours found in rodents after dosing with inhibitors of
acid secretion were reclassified to be of ECL cell origin. The
gastrin receptor is localized to the ECL cell only, where
gastrin stimulates the function and growth.
Drug-induced hypo-acidity induces hypergastrinaemia and ECL cell
hyperplasia responsible for rebound
acid hypersecretion. Every condition with long-term hypergastrinaemia disposes to ECL cell
neoplasia. In man, both
atrophic gastritis and
gastrinoma lead to ECL cell
carcinoids.
Proton pump inhibitors induce hypergastrinaemia with ECL cell
hyperplasia and ECL cell
carcinoids that disappear when stopping treatment. The
gastrin antagonist
netazepide induces regression of ECL cell
carcinoids due to
atrophic gastritis. Human gastric
carcinomas of diffuse type, particularly the signet-ring subtype, show ECL cell differentiation, suggesting involvement of
gastrin in the
carcinogenesis. Helicobacter pylori (Hp) causes
gastritis and
peptic ulcer, and when infecting the antrum only gives a slight hypergastrinaemia with
acid hypersecretion predisposing to
duodenal ulcer, but protecting from
gastric cancer. When Hp
infection spreads to oxyntic mucosa, it induces
atrophy, reduced
acid secretion and marked hypergastrinaemia and
cancer.It is remarkable that the interaction between Hp and
gastrin may explain the pathogenesis of most diseases in the upper gastrointestinal tract.