Cholecystokinin B receptor (CCK2R) (CCK2R)

The Cholecystokinin B receptor (CCK2R), also known as the gastrin receptor, is a G protein-coupled receptor primarily expressed on enterochromaffin-like (ECL) cells in the gastric mucosa and within the central nervous system (UniProt: P32239). In the stomach, gastrin binds to CCK2R on ECL cells to stimulate the release of histamine, which subsequently activates parietal cells to produce gastric acid (StatPearls: Gastrin). Beyond acid regulation, CCK2R signaling promotes the proliferation and differentiation of ECL cells, making it a critical factor in the development of gastric neuroendocrine tumors and ECL cell hyperplasia associated with chronic hypergastrinemia (PMID: 25635140). Therapeutic targeting of CCK2R with antagonists like netazepide aims to reduce gastric acid secretion and inhibit the growth of gastrin-dependent tumors. Conversely, CCK2R agonists are used diagnostically to stimulate acid production or as imaging agents for neuroendocrine tumors. The receptor also plays a role in the central nervous system, where it is involved in modulating anxiety and pain perception. Chronic activation of this receptor by high gastrin levels, often caused by proton pump inhibitor use or gastrinomas, can lead to significant ECL cell expansion. Selective CCK2R antagonists are being investigated as potential treatments for various gastrointestinal malignancies and acid-related disorders.

Other names

Gastrin receptorCholecystokinin-2 receptorCCK-B receptorCCKBR

Antagonism of the CCK2 receptor on enterochromaffin-like (ECL) cells inhibits gastrin-stimulated histamine release and suppresses ECL cell hyperplasia. Agonism stimulates gastric acid secretion.