Cholecystokinin (CCK or CCK-PZ; from Greek chole, "bile"; cysto, "sac"; kinin, "move"; hence, move the bile-sac (gallbladder)) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.
History
Evidence that the small intestine controls the release of bile was uncovered as early as 1856, when French physiologist Claude Bernard showed that when dilute acetic acid was applied to the orifice of the bile duct, the duct released bile into the duodenum. In 1903 the French physiologist showed that this reflex was not mediated by the nervous system. In 1904 the French physiologist Charles Fleig showed that the discharge of bile was mediated by a substance that was conveyed by the blood. There remained the possibility that the increased flow of bile in response to the presence of acid in the duodenum might be due to secretin, which had been discovered in 1902. The problem was finally resolved in 1928 by Andrew Conway Ivy and his colleague Eric Oldberg of the Northwestern University Medical School, who found a new hormone that caused contraction of the gall bladder and that they called "cholecystokinin". In 1943, Alan A. Harper and Henry S. Raper of the University of Manchester discovered a hormone that stimulated pancreatic enzyme secretion and that they named "pancreozymin"; however, pancreozymin was subsequently found to be cholecystokinin. Swedish biochemists Johannes Erik Jorpes and Viktor Mutt undertook the monumental task of isolating and purifying porcine cholecystokinin and then determining its amino acid sequence. They finally presented porcine cholecystokinin's amino acid sequence in 1968.
Structure
Cholecystokinin is a member of the gastrin/cholecystokinin family of peptide hormones and is very similar in structure to gastrin, another gastrointestinal hormone. CCK and gastrin share the same five C-terminal amino acids. CCK is composed of varying numbers of amino acids depending on post-translational modification of the 150-amino acid precursor, preprocholecystokinin. Thus, the CCK peptide hormone exists in several forms, each identified by the number of amino acids it contains, e.g., CCK-58, CCK-33, CCK-22 and CCK-8. CCK58 assumes a helix-turn-helix configuration. Biological activity resides in the C-terminus of the peptide. Most CCK peptides have a sulfate group attached to a tyrosine located seven residues from the C-terminus (see tyrosine sulfation). This modification is crucial for the ability of CCK to activate the cholecystokinin A receptor. Nonsulfated CCK peptides also occur, which consequently cannot activate the CCK-A receptor, but their biological role remains unclear.
Function
CCK plays important physiological roles both as a neuropeptide in the central nervous system and as a peptide hormone in the gut. It is the most abundant neuropeptide in the central nervous system. CCK has been researched thoroughly for its role in digestion and it participates in a number of processes such as digestion, satiety and anxiety.
Gastrointestinal
CCK is synthesized and released by enteroendocrine cells in the mucosal lining of the small intestine (mostly in the duodenum and jejunum), called I cells, neurons of the enteric nervous system, and neurons in the brain. It is released rapidly into the circulation in response to a meal. The greatest stimulator of CCK release is the presence of fatty acids and/or certain in the amino acids in the chyme entering the duodenum. In addition, release of CCK is stimulated by monitor peptide (released by pancreatic acinar cells), CCK-releasing protein (via paracrine signalling mediated by enterocytes in the gastric and intestinal mucosa), and acetylcholine (released by the parasympathetic nerve fibers of the vagus nerve).
Once in the circulatory system, CCK has a relatively short half-life.