cholecystokinin

Cholecystokinin (CCK) is a peptide hormone and neuropeptide that coordinates digestion and satiety. It is produced primarily by enteroendocrine I cells in the mucosa of the duodenum and proximal jejunum. The gene product preprocholecystokinin is proteolytically processed to several active forms, most notably CCK-8, CCK-33, and CCK-58; the relative abundance of forms varies by tissue and physiological state. CCK is released in response to fatty acids, amino acids, and digestion products in chyme, and to neural input from the vagus nerve.

Actions: In the pancreas, CCK stimulates acinar cells to secrete digestive enzymes such as amylase, lipase, and proteases. In the gallbladder, it induces contraction and bile release; it also relaxes the sphincter of Oddi to allow bile and pancreatic juice to flow into the duodenum. CCK slows gastric emptying, helping regulate the rate at which chyme enters the small intestine. In the pancreas, CCK often acts in concert with secretin to optimize digestion.

Receptors and signaling: Peripheral effects are mediated primarily by the CCK1 receptor (also called CCK-A), with CCK2 (CCK-B) receptors more prominent in the brain and stomach. Binding to CCK1 activates Gq signaling, raising intracellular calcium and triggering enzyme secretion and smooth muscle contraction. CCK also acts as a brain and gut neuropeptide, signaling satiety via vagal pathways to the brain.

Clinical and research notes: CCK signaling has been explored as a target for appetite regulation and obesity treatment. CCK-elicited gallbladder contraction is used in diagnostic tests, such as CCK-stimulated cholescintigraphy, to assess gallbladder ejection fraction. Defects or alterations in CCK signaling can contribute to digestive inefficiency or gallbladder disease in some contexts.