CCKBR

CCKBR, or the cholecystokinin B receptor, is a G protein-coupled receptor encoded by the CCKBR gene in humans. It binds the peptide hormones cholecystokinin (CCK) and gastrin with high affinity, with sulfated forms showing particularly strong activity. The receptor is distributed in multiple tissues, notably in the central nervous system (including hippocampus, cortex, and amygdala) and in the stomach, with expression also reported in the pancreas and other parts of the GI tract.

In terms of signaling and function, CCKBR primarily couples to Gq/11 proteins, triggering phospholipase C activation, inositol trisphosphate generation, and increases in intracellular calcium. In the stomach, the receptor contributes to gastrin-induced acid secretion, largely via stimulation of histamine release from enterochromaffin-like cells and subsequent action on parietal cells. In the brain, CCKBR is implicated in modulating neuronal excitability, anxiety, memory, and feeding-related behavior, though the precise roles can vary by brain region and context.

Pharmacology and clinical relevance include the use of selective antagonists, such as L-365,260 and CI-988, in research to dissect CCKBR function. Agonists, including sulfated CCK peptides, are used to probe receptor signaling. Therapeutically and diagnostically, the CCK2 receptor (CCKBR) is a target in certain neuroendocrine tumors, where radiolabeled ligands for imaging and, in some approaches, targeted radionuclide therapy have been explored. Genetic and animal studies continue to clarify CCKBR’s roles in behavior and GI physiology.