View source for Cholecystokinin

{{otherusesof|CCK}} 

{{PBB|geneid=885}}
[[Image:Control-of-stomach-acid-sec.png|thumb|CCK identified at bottom right.]]
'''Cholecystokinin''' ('''CCK''' or '''CCK-PZ'''; from [[Greek language|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 [[enzyme]]s and [[bile]] from the [[pancreas]] and [[gallbladder]], respectively. It also acts as a [[appetite suppressant|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]].<ref name="pmid10866896">{{cite journal | author = Kissin I, Bright CA, Bradley EL | title = Acute tolerance to continuously infused alfentanil: the role of cholecystokinin and N-methyl-D-aspartate-nitric oxide systems | journal = Anesth. Analg. | volume = 91 | issue = 1 | pages = 110–6 | year = 2000 | pmid = 10866896  | doi = 10.1097/00000539-200007000-00021| url = http://www.anesthesia-analgesia.org/cgi/content/abstract/91/1/110}}</ref><ref name="pmid17558184">{{cite journal | author = Fukazawa Y, Maeda T, Kiguchi N, Tohya K, Kimura M, Kishioka S | title = Activation of spinal cholecystokinin and neurokinin-1 receptors is associated with the attenuation of intrathecal morphine analgesia following electroacupuncture stimulation in rats | journal = J. Pharmacol. Sci. | volume = 104 | issue = 2 | pages = 159–66 | year = 2007 | pmid = 17558184 | doi = 10.1254/jphs.FP0070475 }}</ref>

==Structure==
CCK is composed of varying numbers of [[amino acid]]s 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 hormone]]s. CCK and gastrin share the same five amino acids at their C-termini.

==Functions==
CCK mediates a number of [[physiology|physiological]] processes, including [[digestion]] and satiety. It is located in the small intestine, and detects the presence of fat in the chyme. CCK then tells the stomach to slow down the speed of digestion so the small intestine can effectively digest the fats.

===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]], hence the old name ''pancreozymin''. 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 salt]]s form [[Amphipathic lipids|amphipathic]] [[micelle]]s that [[emulsification|emulsify]] fats, aiding in their digestion and absorption.

===Neurobiology===
As a [[neuropeptide]], CCK mediates satiety by acting on the [[CCK receptor]]s 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.  CCK-4 is routinely used to induce anxiety in humans though certainly different forms of CCK are being shown to have highly variable effects.<ref name="pmid9855480">{{cite journal | author = Greenough A, Cole G, Lewis J, Lockton A, Blundell J | title = Untangling the effects of hunger, anxiety, and nausea on energy intake during intravenous cholecystokinin octapeptide (CCK-8) infusion | journal = Physiol. Behav. | volume = 65 | issue = 2 | pages = 303–10 | year = 1998 | pmid = 9855480 | doi = 10.1016/S0031-9384(98)00169-3 }}</ref> The mechanism for this hunger suppression is thought to be a decrease in the rate of gastric emptying.<ref name="pmid3812772">{{cite journal | author = Shillabeer G, Davison JS | title = Proglumide, a cholecystokinin antagonist, increases gastric emptying in rats | journal = Am. J. Physiol. | volume = 252 | issue = 2 Pt 2 | pages = R353–60 | year = 1987 | pmid = 3812772 | doi = | issn = | url =  http://ajpregu.physiology.org/cgi/content/abstract/252/2/R353 }}</ref>

CCK also has stimulatory effects on the [[vagus nerve]], effects that can be inhibited by [[capsaicin]].{{Fact|date=October 2008}} The stimulatory effects of CCK oppose those of [[ghrelin]], which has been shown to inhibit the vagus nerve.{{Fact|date=October 2008}} The CCK tetrapeptide fragment [[CCK-4]] ([[Tryptophan|Trp]]-[[Methionine|Met]]-[[Aspartate|Asp]]-[[Phenylalanine|Phe]]-NH<sub>2</sub>) reliably causes anxiety when administered to humans, and is commonly used in scientific research to induce [[panic attack]]s for the purpose of testing new [[anxiolytic]] drugs.<ref>Bradwejn J. Neurobiological investigations into the role of cholecystokinin in panic disorder. ''Journal of Psychiatry and Neuroscience''. 1993 Jul;18(4):178-88. PMID 8104032</ref>

The effects of CCK vary between individuals. For example, in [[rat]]s, 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.<ref name="pmid9835394">{{cite journal | author = Fink H, Rex A, Voits M, Voigt JP | title = Major biological actions of CCK--a critical evaluation of research findings | journal = Exp Brain Res | volume = 123 | issue = 1-2 | pages = 77–83 | year = 1998 | pmid = 9835394 | doi = 10.1007/s002210050546 }}</ref>

==Interactions==
Cholecystokinin has been shown to [[Protein-protein_interaction|interact]] with [[Cholecystokinin B receptor]].<ref name=pmid15520004>{{cite journal |last=Harikumar |first=Kaleeckal G |authorlink= |coauthors=Clain Jeremy, Pinon Delia I, Dong Maoqing, Miller Laurence J |year=[[2005]]|month=Jan. |title=Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy |journal=J. Biol. Chem. |volume=280 |issue=2 |pages=1044–50 |publisher= |location = United States| issn = 0021-9258| pmid = 15520004 |doi = 10.1074/jbc.M409480200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name=pmid15001692>{{cite journal |last=Aloj |first=Luigi |authorlink= |coauthors=Caracò Corradina, Panico Mariarosaria, Zannetti Antonella, Del Vecchio Silvana, Tesauro Diego, De Luca Stefania, Arra Claudio, Pedone Carlo, Morelli Giancarlo, Salvatore Marco |year=[[2004]]|month=Mar. |title=In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging |journal=J. Nucl. Med. |volume=45 |issue=3 |pages=485–94 |publisher= |location = United States| issn = 0161-5505| pmid = 15001692 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref><ref name=pmid12695525>{{cite journal |doi=10.1124/mol.63.5.973 |last=Galés |first=Céline |authorlink= |coauthors=Poirot Marc, Taillefer Julien, Maigret Bernard, Martinez Jean, Moroder Luis, Escrieut Chantal, Pradayrol Lucien, Fourmy Daniel, Silvente-Poirot Sandrine |year=[[2003]]|month=May. |title=Identification of tyrosine 189 and asparagine 358 of the cholecystokinin 2 receptor in direct interaction with the crucial C-terminal amide of cholecystokinin by molecular modeling, site-directed mutagenesis, and structure/affinity studies |journal=Mol. Pharmacol. |volume=63 |issue=5 |pages=973–82 |publisher= |location = United States| issn = 0026-895X| pmid = 12695525 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>

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]].<ref>{{cite journal |last=Gurda |first=Grzegorz T. |authorlink= |coauthors=Guo LiLi, Lee Sae-Hong, Molkentin Jeffery D, Williams John A |year=[[2008]]|month=Jan. |title=Cholecystokinin Activates Pancreatic Calcineurin-NFAT Signaling In Vitro and In Vivo |journal=Mol. Biol. Cell. |volume=19 |issue=198-206 |pages=198–205 |publisher= |location = United States| issn = | pmid = 17978097 |doi = 10.1091/mbc.E07-05-0430| bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=2174201 }}</ref>

==See also==
* [[Antianalgesia]]
* [[Cholecystokinin antagonist]]
* [[Proglumide]]

==References==
{{Reflist|2}}

==External links==
* {{MeshName|Cholecystokinin}}

{{Hormones}}
{{Gastrointestinal physiology}}
{{Neuropeptides}}
{{Gastrointestinal hormones}}

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[[Category:Anxiogenics]]
[[Category:Hepatology]]
[[Category:Intestinal hormones]]
[[Category:Neuropeptides]]
[[Category:Cholecystokinin]]

[[de:Cholecystokinin]]
[[dv:ކޯލިސިސްޓަކައިނިން]]
[[es:Colecistoquinina]]
[[fr:Cholécystokinine]]
[[hr:Kolecistokinin]]
[[it:Colecistochinina]]
[[he:כוליציסטוקינין]]
[[nl:Cholecystokinine]]
[[ja:コレシストキニン]]
[[pl:Cholecystokinina]]
[[pt:Colecistocinina]]
[[ru:Холецистокинин]]
[[sr:Холецистокинин]]
[[fi:Kolekystokiniini]]
[[sv:Cholecystokinin]]
[[Category:2Fix]]