Cholecystokinin A receptor (CCKAR) (CCKAR)

The Cholecystokinin A receptor (CCKAR), also known as the CCK1 receptor, is a G protein-coupled receptor that serves as the primary molecular mediator of gallbladder contraction. Located on the smooth muscle cells of the gallbladder and within the pancreas, CCKAR is activated by the peptide hormone cholecystokinin (CCK) released from the duodenum in response to dietary fats and proteins (StatPearls, 2023). This activation triggers a signaling cascade involving Gq proteins and intracellular calcium mobilization, resulting in the forceful contraction of the gallbladder and the subsequent ejection of bile into the small intestine (UniProt, P32238). Clinically, CCKAR is targeted by diagnostic agents like sincalide to evaluate gallbladder motility and by various experimental compounds for treating obesity and gastrointestinal disorders (PubChem, CID 5460233). Impairments in CCKAR-mediated contraction are linked to the formation of gallstones (cholelithiasis) and biliary dyskinesia, highlighting its critical role in hepatobiliary health (PubMed, 15611038). Beyond its role in digestion, CCKAR signaling in the central and peripheral nervous systems contributes to the regulation of gastric emptying and the induction of satiety. Therapeutic strategies targeting this receptor include agonists for diagnostic imaging and potential weight management, as well as antagonists for treating certain types of pain or motility issues.

Other names

CCK1 receptorCCK-A receptorCholecystokinin-1 receptorCCK1RCholecystokinin receptor type A

CCKAR agonists bind to the receptor on gallbladder smooth muscle cells, activating the Gq/11 signaling pathway and phospholipase C, which increases intracellular calcium levels and triggers muscle contraction and bile ejection.