CCKBR

CCKBR (cholecystokinin B receptor), also known as CCK2R, is a class A G protein-coupled receptor that binds both gastrin and cholecystokinin and is predominantly expressed in the central nervous system and gastrointestinal tract, where it regulates neuropeptide signaling and gastric physiological responses^[1]. Mechanistically, CCKBR couples to G proteins that activate phosphatidylinositol-calcium signaling and phospholipase C-dependent pathways, thereby controlling intracellular calcium mobilization and downstream cellular responses^[1]. Structural studies further demonstrated ligand-specific recognition and receptor activation mechanisms, providing a molecular framework for understanding peptide selectivity and signal transduction within the cholecystokinin receptor family. In disease-associated settings, aberrant CCKBR transcripts and splice variants have been identified in colorectal and pancreatic tumor cells, supporting a role for altered receptor signaling in tumor biology^[1][2]. Compared with the related isoform CCKAR (CCK1R), CCKBR exhibits high affinity for both sulfated and nonsulfated gastrin/CCK peptides and shows a distinct tissue distribution enriched in the brain and stomach, highlighting functional divergence between receptor subtypes^[3]. Alternative receptor isoforms have also been reported, including constitutively active variants that may promote gastrin-independent proliferative signaling, making isoform-specific characterization important for mechanistic studies^[2]. For experimental applications, selective CCKBR antagonists, including L-365,260 and related compounds, have been widely used to investigate receptor-mediated regulation of neurotransmission, pain processing, anxiety-related pathways, and gastrointestinal signaling^[3].