What is the most potent stimulus for hydrochloric acid (HCl) release from parietal cells?

The release of hydrochloric acid (HCl) from parietal cells in the stomach is stimulated by several factors, but histamine and acetylcholine (ACh) are considered the most potent stimulants in this process.

Histamine, which is produced by enterochromaffin-like cells in the gastric mucosa, binds to H2 receptors on parietal cells, leading to increased production of cAMP and subsequent stimulation of proton pumps that secrete HCl. Acetylcholine, on the other hand, is released by vagal nerve endings and acts on muscarinic receptors on parietal cells. This action also stimulates acid secretion and enhances the effects of histamine.

In contrast, while gastrin is a significant hormone that promotes gastric acid secretion by stimulating both parietal cells and the release of histamine from enterochromaffin-like cells, its action is ultimately mediated through these other mechanisms rather than acting directly on the parietal cells as histamine and ACh do. Cholecystokinin primarily plays a role in fat digestion and has less direct impact on gastric acid secretion, while somatostatin generally inhibits gastric secretions, acting as a regulatory mechanism to prevent excessive acid production.

Therefore,