cholecystokinin

Cholecystokinin
Identifiers
Symbols	CCK; MGC117187
External IDs	OMIM: 118440 MGI: 88297 HomoloGene: 583
Gene ontology Molecular function • neuropeptide hormone activity Cellular component • extracellular region • soluble fraction • axon Biological process • neuron migration • signal transduction • axonogenesis • eating behavior
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	885	12424
Ensembl	ENSG00000187094	ENSMUSG00000032532
UniProt	P06307	Q53WS9
RefSeq	NM_000729 (mRNA)	NM_031161 (mRNA)
	NP_000720 (protein)	NP_112438 (protein)
Location	Chr 3: 42.27 - 42.28 Mb	Chr 9: 121.34 - 121.34 Mb
PubMed search	[1]	[2]

CCK identified at bottom right.

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, previously called pancreozymin, is synthesised by I-cells in the mucosal epithelium of the small intestine and secreted in the duodenum, the first segment of the small intestine, and causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively. It also acts as a hunger suppressant. Recent evidence has suggested that it also plays a major role in inducing drug tolerance to opioids like morphine and heroin, and is partly implicated in experiences of pain hypersensitivity during opioid withdrawal.^[1][2]

Structure

CCK is composed of varying numbers of amino acids depending on post-translational modification of the CCK gene product, preprocholecystokinin. Thus CCK is actually a family of hormones identified by number of amino acids, e.g., CCK58, CCK33, and CCK8. CCK58 assumes a helix-turn-helix configuration. Its existence was first suggested in 1905 by the British physiologist Joy Simcha Cohen. CCK is very similar in structure to gastrin, another of the gastrointestinal hormones. CCK and gastrin share the same five amino acids at their C-termini.

Functions

CCK mediates a number of physiological processes, including digestion and satiety.

Digestion

Secretion of CCK by the duodenal and intestinal mucosa is stimulated by fat- or protein-rich chyme entering the duodenum. It then inhibits gastric emptying and gastric acid secretion and mediates digestion in the duodenum. It stimulates the acinar cells of the pancreas to release water and ions and stimulates the secretion of a juice rich in pancreatic digestive enzymes. Together these enzymes catalyze the digestion of fat, protein, and carbohydrates. Thus, as the levels of the substances that stimulated the release of CCK drop, the concentration of the hormone drops as well. The release of CCK is also inhibited by somatostatin.

CCK also causes the increased production of hepatic bile, and stimulates the contraction of the gall bladder and the relaxation of the Sphincter of Oddi (Glisson's sphincter), resulting in the delivery of bile into the duodenal part of the small intestine. Bile salts form amphipathic micelles that emulsify fats, aiding in their digestion and absorption.

Neurobiology

As a neuropeptide, CCK mediates satiety by acting on the CCK receptors distributed widely throughout the central nervous system. In humans, it has been suggested that CCK administration causes nausea and anxiety, and induces a satiating effect. Some studies have given a strong correlation for the satiating effect, but have not proven or disproven that CCK administration causes nausea or anxiety.^[3] The mechanism for this hunger suppression is thought to be a decrease in the rate of gastric emptying.^[4]

CCK also has stimulatory effects on the vagus nerve, effects that can be inhibited by capsaicin.^{[citation needed]} The stimulatory effects of CCK oppose those of ghrelin, which has been shown to inhibit the vagus nerve.^{[citation needed]} The CCK tetrapeptide fragment CCK-4 (Trp-Met-Asp-Phe-NH₂) reliably causes anxiety when administered to humans, and is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.^[5]

The effects of CCK vary between individuals. For example, in rats, CCK administration significantly reduces hunger in young males, but is slightly less effective in older subjects, and even slightly less effective in females. The hunger-suppressive effects of CCK also are reduced in obese rats.^[6]

Interactions

Cholecystokinin has been shown to interact with Cholecystokinin B receptor.^[7][8][9]

CCK has also been shown to interact with calcineurin in the pancreas. Calcineurin will go on to activate the transcription factors NFAT 1-3, which will stimulate hypertrophy and growth of the pancreas. CCK can be stimulated by a diet high in protein, or by protease inhibitors.^[10]

See also

• Antianalgesia
• Cholecystokinin antagonist
• Proglumide

References

External links

• MeSH Cholecystokinin