“The exact mechanism of gastric acid secretion has yet to be elucidated. It is known that four endogenous substances
- Acetylcholine, the neurotransmitter of the vagus nerve;
- Gastrin, a systemic hormone secreted by G cells in the antrum of the stomach;
- Histamine, a paracrine hormone secreted by enterochromasin cells in the walls of the stomach; and
- Calcium
all stimulate acid secretion.
There are receptors for acetylcholine (muscarinic receptors), gastrin (gastrin receptors), and histamine (H2-receptors. Calcium may both increase gastrin and act as a second messenger for gastrin and acetylcholine. Histamine probably activates adenylate cyclase, which converts cytosolic ATP to cAMP, which acts as a second messenger. There is some evidence that histamine may act as the common mediator of acid secretion, since it augments acetylcholine- and gastrin-stimulated secretion, and H2-blockers inhibit both acetylcholine and gastrin-stimulated secretion.
The final common pathway of acid secretion is the proton pump, Na+ / K+ ATPase. The physiological essence of the Na+ / K+ ATPase is to exchange K+ for H+; H+ is secreted against a profound concentration gradient of 2,000,000:1 or greater. This acid secretion is stimulated by the sight, smell, and ingestion of food. In addition to the stimulated acid secretion, there is a basal acid secretion that occurs independently of eating. An important feature of the basal acid secretion is its diurnal variation, such that acid secretion is low during the day but relatively high at night–generally peaking between 10:00 PM and midnight. For this reason, patients tend to wake up around midnight with dyspepsia and heartburn. It is at this time that gastric pH tends to drop to 1 or 2, since acid secretion is relatively high and is not neutralized by food.
During the day, the food that stimulates acid secretion also neutralizes it, keeping the gastric pH about 4 or 5. The diurnal variation in acid secretion forms the rationale for using H2-receptor antagonists as a single evening dose in the treatment of gastric and duodenal ulcers.
As discussed above, PGE2 acts both to inhibit acid secretion and increase mucosal protection. There are other inhibitors of acid secretion. Somatostatin and secretin are probably the most important under physiological conditions.” From Remington
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC424132/
Remington: The Science and Practice of Pharmacy. Edited by David B. Troy, Paul Beringer.