Review article: current perspectives on hypergastrinaemia and enterochromaffin-like-cell hyperplasia.
Rabeprazole, a new benzimidazole proton pump inhibitor (PPI), is among a class of agents known to be very potent inhibitors of gastric acid secretion. PPIs inhibit hydrogen-potassium adenosine triphosphatase activity on the luminal surface of the parietal cell, effectively blocking the final common pathway for gastric acid secretion. Raising gastric pH stimulates the production of gastrin by G cells in the antrum of the stomach, which can lead to enterochromaffin-like (ECL)-cell hyperplasia. In the past, these changes have been viewed with concern, particularly in the light of studies in rats indicating that hypergastrinaemia and ECL-cell hyperplasia induce gastric carcinoid tumour formation. All available clinical data indicate that long-term PPI use does not lead to carcinoid tumour formation in humans. In fact, both serum gastrin elevation and ECL-cell hyperplasia are now generally viewed as normal physiological responses to gastric acid suppression. Serum gastrin concentrations, in particular, correlate well with gastric acid suppression, which has led to the use of gastrin response by some investigators as a surrogate marker of antisecretory effectiveness. Long-term tolerability data indicate that PPIs have a favourable side-effect profile. Data obtained from patients receiving acute or long-term maintenance rabeprazole therapy support this conclusion. Furthermore, neither animal nor human data obtained with rabeprazole suggest a significant risk for neoplastic changes secondary to hypergastrinaemia.
Robinson
M
M
University of Oklahoma College of Medicine, Oklahoma Foundation for Digestive Research, Oklahoma City, USA. malcolm-robinson@ouhsc.edu
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D019861:Enterochromaffin-like Cells / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005755:Gastrins / Q000097:blood*; D006801:Humans; D006965:Hyperplasia; D009853:Omeprazole / Q000031:analogs & derivatives; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005755:Gastrins; D064750:Rabeprazole; D009853:Omeprazole