Cholecystokinin receptor 1 (CCK1R (also known as CCKAR))

Cholecystokinin receptor 1 is a G protein-coupled receptor primarily expressed in the pancreas, gallbladder, gastrointestinal tract muscles/nerves, and certain brain regions. It binds sulfated cholecystokinin peptides with high affinity—especially those containing a sulfated tyrosine residue—and mediates key physiological processes such as pancreatic enzyme secretion, gallbladder contraction, regulation of gastrointestinal motility, and control of food intake via central mechanisms influencing satiety. The gene encoding this protein is located on chromosome 4p15.1-p15.2. CCK1R signals mainly through Gq/11 proteins but can also couple with other transducers like Gs or arrestins under some conditions; its pleiotropic signaling affects multiple downstream effectors including phospholipase C/Ca²⁺ mobilization as well as MAPK/ERK pathways[2][3][5]. Pharmacological agents targeting this pathway have been explored for treating obesity/metabolic syndrome by modulating appetite but have not achieved widespread clinical use due to variable efficacy—particularly reduced response observed in obese individuals with altered membrane cholesterol content impairing canonical signal transduction from the receptor[5].

Other names

Cholecystokinin A receptorCCK-A receptorCCKARCCK 1 receptor

Agonists stimulate the receptor to activate Gq/11 proteins, leading to phospholipase C activation and increased intracellular calcium. This results in pancreatic enzyme secretion, gallbladder contraction, and modulation of neuronal signaling related to satiety. Antagonists block these effects by inhibiting ligand binding or downstream signaling pathways[2][5].