Cholecystokinin
From DrugPedia: A Wikipedia for Drug discovery
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[edit] Description
Cholecystokinin (CCK; 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.<ref name="pmid10866896">Kissin I, Bright CA, Bradley EL (2000). "Acute tolerance to continuously infused alfentanil: the role of cholecystokinin and N-methyl-D-aspartate-nitric oxide systems". Anesth. Analg. 91 (1): 110–6. doi:. PMID 10866896.</ref><ref name="pmid17558184">Fukazawa Y, Maeda T, Kiguchi N, Tohya K, Kimura M, Kishioka S (2007). "Activation of spinal cholecystokinin and neurokinin-1 receptors is associated with the attenuation of intrathecal morphine analgesia following electroacupuncture stimulation in rats". J. Pharmacol. Sci. 104 (2): 159–66. doi:. PMID 17558184.</ref>
[edit] 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 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.
[edit] Functions
CCK mediates a number of physiological processes, including digestion and satiety.
[edit] 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 acinar cell of 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 the levels of the substances which stimulated the release of CCK drop and 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.
[edit] 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 weakly decreases the desire to eat is the reason for CCK administration to induce 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.<ref name="pmid9855480">Greenough A, Cole G, Lewis J, Lockton A, Blundell J (1998). "Untangling the effects of hunger, anxiety, and nausea on energy intake during intravenous cholecystokinin octapeptide (CCK-8) infusion". Physiol. Behav. 65 (2): 303–10. doi:. PMID 9855480.</ref> The mechanism for this hunger suppression is thought to be a decrease in the rate of gastric emptying.<ref name="pmid3812772">Shillabeer G, Davison JS (1987). "Proglumide, a cholecystokinin antagonist, increases gastric emptying in rats". Am. J. Physiol. 252 (2 Pt 2): R353–60. PMID 3812772.</ref>
CCK also has stimulatory effects on the vagus nerve, effects that can be inhibited by capsaicin.Template:Fact The stimulatory effects of CCK oppose those of ghrelin, which has been shown to inhibit the vagus nerve.Template:Fact 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.<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 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.<ref name="pmid9835394">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. doi:. PMID 9835394.</ref>
[edit] Source Organism
Gallus gallus (Chicken).
[edit] Taxomomy
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves;Neognathae; Galliformes; Phasianidae; Phasianinae; Gallus.
[edit] Subcellular Localization
Secreted.
[edit] Developmental Stage
[edit] Similarity
Belongs to the gastrin/cholecystokinin family.
[edit] Post translational Modification
The precursor is cleaved by enzymes to produce a number of active cholecystokinins.
[edit] Function
This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. It also decreases food intake and regulates gastrointestinal physiological processes.
[edit] GeneID
414884
