Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.

In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds to M3 receptors on these cells. This binding in ECL cells stimulates the release of histamine, which interacts with H2 receptors in the parietal cells. In parietal cells, the binding of gastrin and acetylcholine to their respective receptors activates Gq proteins and phospholipase C, which turns phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol. IP3 binds to receptors on the endoplasmic reticulum, releasing calcium ions into the cytoplasm. The increased Ca²⁺ concentration activates protein kinases, stimulating the proton pump and inducing acid secretion.

Additionally, acetylcholine and histamine binding in parietal cells initiate the Gs-adenylyl cyclase-cAMP-PKA pathway. This process stimulates the Gs protein, activating adenylyl cyclase to convert ATP into cAMP. Increased cAMP levels activate protein kinase A, triggering the proton pump to produce hydrochloric acid. Balancing gastric acid and pepsin secretion with mucosal defense mechanisms is vital for stomach health. However, conditions like H. pylori infection and prolonged NSAID use can disrupt this balance, causing overproduction of gastric acid and pepsin. These factors erode the protective mucosal lining and contribute to ulceration.