H2receptor

The H2 receptor, also known as the histamine H2 receptor, is a class A G protein-coupled receptor that binds histamine. In humans it is encoded by the HRH2 gene. The receptor is expressed in gastric parietal cells, where its activation stimulates gastric acid secretion, and it is also found in other tissues such as cardiac tissue, brain, and various immune cells, where it can influence inflammatory, cardiovascular, and other physiological processes.

Signal transduction through the H2 receptor primarily involves coupling to the Gs protein, which activates adenylyl cyclase and increases intracellular cyclic AMP. The rise in cAMP activates protein kinase A, promoting the activity and trafficking of the H+/K+-ATPase proton pump to the apical membrane of parietal cells and thereby enhancing acid secretion. Receptor desensitization can occur with prolonged exposure to histamine.

Pharmacology and clinical use center on H2 receptor antagonists, which block histamine binding and reduce gastric acid production. Clinically used drugs include famotidine, nizatidine, and cimetidine, with ranitidine having reduced use in some regions due to safety concerns. Indications include gastroesophageal reflux disease (GERD), peptic ulcers, gastritis, and NSAID-induced ulcers; H2 blockers may be used in the management of Zollinger-Ellison syndrome as part of acid-suppressive therapy. Cimetidine can interact with other drugs by inhibiting hepatic cytochrome P450 enzymes and may cause antiandrogenic effects; most H2 antagonists are generally well tolerated.

Genetic variations in HRH2 can influence receptor function and histamine signaling, with potential implications for gastric acid secretion and response to therapy. The H2 receptor thus plays a key role in regulating gastric physiology and in the pharmacologic management of acid-related disorders.