From the Guidelines
Stomach acid production is a complex process involving the hydrogen-potassium ATPase pump (H+/K+ ATPase) in parietal cells, regulated by histamine, acetylcholine, and gastrin, which can be disrupted by rebound acid hypersecretion after prolonged proton pump inhibitor (PPI) therapy. The mechanism of stomach acid production involves the action of the proton pump, which transports hydrogen ions from the cytoplasm of parietal cells into the stomach lumen in exchange for potassium ions, creating an acidic environment with a pH between 1.5 and 3.5. This process is regulated by multiple stimuli, including:
- Histamine, released by enterochromaffin-like cells, which binds to H2 receptors on parietal cells
- Acetylcholine, from vagal nerve stimulation, which binds to muscarinic receptors
- Gastrin, released by G cells in response to proteins, which stimulates acid secretion both directly and by promoting histamine release These pathways converge to activate the proton pump through intracellular signaling involving cAMP and calcium, as described in the context of PPI therapy and its effects on gastric acid production 1. The study by 1 highlights the importance of understanding the mechanism of stomach acid production, particularly in the context of rebound acid hypersecretion (RAHS) after prolonged PPI therapy, which can lead to transient upper GI symptoms due to the increased capacity of the stomach to produce acid.
From the FDA Drug Label
Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production.
The mechanism of stomach acid production involves the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell, which is regarded as the acid (proton) pump within the gastric mucosa. This enzyme system is responsible for the final step of acid production. 2
From the Research
Mechanism of Stomach Acid Production
The production of stomach acid is a complex process involving multiple stimulants and cell types. The main stimulants of acid secretion are:
- Gastrin, released from antral G cells 3, 4
- Histamine, released from oxyntic enterochromaffin-like cells 3, 4, 5, 6
- Acetylcholine, released from antral and oxyntic intramural neurons 3, 4
Role of Gastrin and Histamine
Gastrin acts on CCK2 receptors to control the synthesis of ECL-cell histamine, which in turn stimulates the parietal cells to secrete HCl 5. The gastrin-ECL cell pathway plays a crucial role in the regulation of gastric acid secretion.
Anatomical Location of ECL Cells
ECL cells are located near the basement membranes in the gastric oxyntic region and are in contact with both chief cells and parietal cells in the same glandular epithelium 6. This close proximity suggests that ECL cells have a paracrine effect on chief cells and parietal cells, and may play an important role in pepsinogen secretion.
Regulation of Acid Secretion
The regulation of acid secretion is a complex process involving multiple factors, including:
- Neuroendocrine regulation: Gastrin, histamine, and acetylcholine stimulate acid secretion 3, 4
- Intracellular regulation: The synthesis and release of histamine from ECL cells is regulated by gastrin and other factors 5
- Hormonal regulation: Ghrelin and coffee stimulate acid secretion, while somatostatin, cholecystokinin, glucagon-like peptide-1, and atrial natriuretic peptide inhibit acid secretion 4