Cholecystokinin receptor type 1 (CCK1R) (CCK1R)

The Cholecystokinin receptor type 1 (CCK1R), also known as the CCK-A receptor, is a G protein-coupled receptor that serves as a primary mediator of the physiological effects of the peptide hormone cholecystokinin (CCK) [1, 10]. It is predominantly expressed in the gastrointestinal tract, including the gallbladder, pancreas, and stomach, as well as in specific regions of the central and peripheral nervous systems [2, 12]. Biologically, CCK1R regulates critical digestive functions such as gallbladder contraction, pancreatic enzyme secretion, and the slowing of gastric emptying to optimize nutrient absorption [8, 11]. It also plays a vital role in the regulation of energy homeostasis by transmitting postprandial satiety signals to the brain [6, 9]. In clinical contexts, dysregulation of CCK1R signaling is implicated in obesity, gallstone formation, and functional gastrointestinal disorders like irritable bowel syndrome [5, 15]. Pharmacological efforts have focused on developing CCK1R agonists for obesity treatment and antagonists for motility disorders, though clinical success has been tempered by challenges in balancing efficacy with safety concerns such as biliary colic and gastrointestinal side effects [11, 16].

Other names

Cholecystokinin A receptorCCK-A receptorCCKARCCK-ARCCK1 receptorCCKRA

Drugs targeting the CCK1 receptor primarily act as either agonists or antagonists. Agonists, such as Sincalide, mimic the action of endogenous cholecystokinin to stimulate gallbladder contraction and pancreatic secretion for diagnostic purposes or to induce satiety for weight management [8, 11]. Antagonists, such as Devazepide and Loxeglumide, competitively bind to the receptor to inhibit its activation, thereby modulating gastrointestinal motility and reducing pancreatic overstimulation, which is explored for treating irritable bowel syndrome and pancreatic disorders [4, 6, 16].