Physiology of cholecystokinin
- Rodger A Liddle, MD
Rodger A Liddle, MD
- Professor of Medicine
- Duke University Medical School
Cholecystokinin (CCK) is the major hormone responsible for gallbladder contraction and pancreatic enzyme secretion. CCK, like other gastrointestinal hormones, is produced in discrete endocrine cells that line the mucosa of the small intestine . It is also found in the central nervous system and peripheral nerves innervating the intestine. In these locations, CCK probably functions as a neurotransmitter.
The original discovery of CCK in 1928 was based upon the observation that a substance within intestinal extracts stimulated gallbladder contraction in dogs (hence the name cholecystokinin). In 1943, a similar extract (which has been called pancreozymin) was noted to stimulate pancreatic enzyme secretion. However, purification of the hormone and determination of its amino acid sequence showed that the actions on the gallbladder and pancreas were due to the same hormone .
Advances in protein biochemistry, molecular biology, and the development of specific CCK receptor antagonists have increased our understanding of the physiologic and potential pathophysiologic actions of CCK. In humans, physiologic properties of CCK include the ability to stimulate gallbladder contraction, increase pancreatic enzyme secretion, delay gastric emptying, potentiate insulin secretion, and regulate food intake (table 1). In addition, CCK regulates bowel motility and has growth promoting effects on the pancreas in certain animals [3,4].
A number of molecular forms of cholecystokinin (CCK) have been identified in brain, intestine, and blood of experimental animals and humans. The original form of CCK purified was a tritriacontapeptide (CCK-33) . CCK is produced from a single gene, and different molecular forms are the result of posttranslational processing. Molecular forms ranging in size from 4 to 83 amino acids have been identified in tissue and blood with the predominant molecular form being CCK-58, and less commonly CCK-8 and CCK-33. (See "Synthesis, secretion, and regulation of gastrointestinal peptides".)
CCK possesses a five amino acid sequence at the carboxyl terminus that is identical to that of gastrin (figure 1). The carboxyl terminus confers the biologic activity of CCK; as a result, gastrin has weak CCK-like activity and CCK has weak gastrin-like activity. The amino acid sequence similarity has also made assays for CCK difficult, since antibodies specific for the biologically active end of the molecule often crossreact with gastrin, which circulates in the blood at concentrations 10 to 100 times greater than that of CCK . (See "Physiology of gastrin".)
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