(Thr²?,Nle³¹)-CCK-9, non-oxidable analog of CCK-9.

Definition

Cholecystokinin (CCK), also called pancreozymin, is a peptide hormone in the small intestine that constitutes the classical gut hormone triad together with gastrin and secretin1. CCK is secreted into the blood following ingestion of a meal and plays a critical role in the ingestion, absorption, intestinal motility, satiety signaling, inhibition of gastric acid secretion and digestion of food1.

Discovery

CCK was discovered in 1928 because of its ability to induce gallbladder contraction2.

Classification

CCK is a neuropeptide.  It is a family of hormones identified by the number of amino acids, for eg: CCK58 and CCK331. 

Structural Characteristics

Prepro-CCK is a115 amino acid peptide that is first cleaved to pro-CCK which in turn results in CCK58, the major processed form of CCK3.  CCK58 assumes a helix-turn-helix configuration3.

Mode of action

CCK binds to CCK receptors on the cell membrane that when activated increase the turnover of phosphatidyl inositol which results in the release of intracellular calcium4.  The calcium released causes increased enzyme secretion either directly or through activation of protein kinase C4.

Functions

CCK induces the gall bladder to contract and eject bile into the intestine5. It stimulates the acinar cells of the pancreas to release water and ions and stimulates the secretion of a juice rich in pancreatic digestive enzymes5. It is known to induce growth of the exocrine pancreas and to stimulate insulin secretion5. CCK is the most abundant neuropeptide in the human brain where it induces panic attacks that are antagonized by a central cholecystokinin receptor antagonist6. ProCCK is expressed in certain neuroendocrine tumors and sarcomas, and the secretion of CCK is impaired in celiac disease and bulimia nervosa7.

References

1.     Fink H, Rex A, Voits M, Voigt JP (1998). Major biological actions of CCK--a critical evaluation of research findings. Exp Brain Res., 123 (1-2), 77–83.

2.     Hunt, J. N. (1948). A method for estimating peptic activity in gastric contents. Biochem. J., 42, 104-109.

3.     Book: Neuropeptides By Fleur L. Strand, 387-389.

4.     Dufresne M, Seva C, Fourmy D (2006). Cholecystokinin and gastrin receptors. Physiol. Rev., 86 (3), 805–47.

5.     Chandra R, Liddle RA (2007). Cholecystokinin. Curr Opin Endocrinol Diabetes Obes., 14(1), 63-7.

6.     Rehfeld JF, Friis-Hansen L, Goetze JP, Hansen TV (2007). The biology of cholecystokinin and gastrin peptides. Curr Top Med Chem, 7(12), 1154-65.

7.     Rehfeld JF (2004). Clinical endocrinology and metabolism. Cholecystokinin. Best Pract Res Clin Endocrinol Metab., 18(4), 569-86.