Cholecystokinin

Last updated

CCK
Identifiers
Aliases CCK , cholecystokinin
External IDs OMIM: 118440; MGI: 88297; HomoloGene: 583; GeneCards: CCK; OMA:CCK - orthologs
Orthologs
SpeciesHumanMouse
Entrez

885

12424

Ensembl

ENSG00000187094

ENSMUSG00000032532

UniProt

P06307

P09240

RefSeq (mRNA)

NM_000729
NM_001174138

NM_031161
NM_001284508

RefSeq (protein)

NP_000720
NP_001167609

NP_001271437
NP_112438

Location (UCSC) Chr 3: 42.26 – 42.27 Mb Chr 9: 121.32 – 121.32 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively. [5] [6]

Contents

History

Evidence that the small intestine controls the release of bile was uncovered as early as 1856, when French physiologist Claude Bernard showed that when dilute acetic acid was applied to the orifice of the bile duct, the duct released bile into the duodenum. [7] [8] In 1903, the French physiologist Émile Wertheimer  [ fr ] showed that this reflex was not mediated by the nervous system. [9] In 1904, the French physiologist Charles Fleig showed that the discharge of bile was mediated by a substance that was conveyed by the blood. [10] There remained the possibility that the increased flow of bile in response to the presence of acid in the duodenum might be due to secretin, which had been discovered in 1902. The problem was finally resolved in 1928 by Andrew Conway Ivy and his colleague Eric Oldberg of the Northwestern University Medical School, who found a new hormone that caused contraction of the gall bladder and that they called "cholecystokinin". [11] In 1943, Alan A. Harper and Henry S. Raper of the University of Manchester discovered a hormone that stimulated pancreatic enzyme secretion and that they named "pancreozymin"; [12] however, pancreozymin was subsequently found to be cholecystokinin. [13] [14] [15] Swedish biochemists Johannes Erik Jorpes and Viktor Mutt undertook the monumental task of isolating and purifying porcine cholecystokinin and then determining its amino acid sequence. They finally presented porcine cholecystokinin's amino acid sequence in 1968. [16]

Structure

Cholecystokinin is a member of the gastrin/cholecystokinin family of peptide hormones and is very similar in structure to gastrin, another gastrointestinal hormone. CCK and gastrin share the same five C-terminal amino acids. CCK is composed of varying numbers of amino acids depending on post-translational modification of the 150-amino acid precursor, preprocholecystokinin. [17] Thus, the CCK peptide hormone exists in several forms, each identified by the number of amino acids it contains, e.g., CCK-58, CCK-33, CCK-22 and CCK-8. CCK58 assumes a helix-turn-helix configuration. [18] Biological activity resides in the C-terminus of the peptide. Most CCK peptides have a sulfate group attached to a tyrosine located seven residues from the C-terminus (see tyrosine sulfation). [17] This modification is crucial for the ability of CCK to activate the cholecystokinin A receptor. Nonsulfated CCK peptides also occur, which consequently cannot activate the CCK-A receptor, but their biological role remains unclear. [17] [19]

Function

CCK plays important physiological roles both as a neuropeptide in the central nervous system and as a peptide hormone in the gut. [20] It is the most abundant neuropeptide in the central nervous system. [21] [22] CCK has been researched thoroughly for its role in digestion [23] In addition to its role in digestion, CCK is involved in regulating various behavioral phenomena, including satiety, appetite, anxiety, thermoregulation, sexual behavior, memory, and the response to drugs of abuse, particularly within the cortex and limbic regions of the brain. [24]

Gastrointestinal

CCK is synthesized and released by enteroendocrine cells in the mucosal lining of the small intestine (mostly in the duodenum and jejunum), called I cells, neurons of the enteric nervous system, and neurons in the brain. [5] It is released rapidly into the circulation in response to a meal. The greatest stimulator of CCK release is the presence of fatty acids and/or certain amino acids in the chyme entering the duodenum. [17] In addition, release of CCK is stimulated by monitor peptide (released by pancreatic acinar cells), CCK-releasing protein (via paracrine signalling mediated by enterocytes in the gastric and intestinal mucosa), and acetylcholine (released by the parasympathetic nerve fibers of the vagus nerve). [25]

Once in the circulatory system, CCK has a relatively short half-life. [26]

Digestion

CCK mediates digestion in the small intestine by inhibiting gastric emptying. It stimulates the acinar cells of the pancreas to release a juice rich in pancreatic digestive enzymes (hence an alternate name, pancreozymin) that 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 and pancreatic peptide. Trypsin, a protease released by pancreatic acinar cells, hydrolyzes CCK-releasing peptide and monitor peptide, in effect turning off the additional signals to secrete CCK. [27]

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. [5] [6] Bile salts form amphipathic lipids, micelles that emulsify fats, aiding in their digestion and absorption. [5]

Effects of cholecystokinin on the gastrointestinal tract. Cholecystokinin is secreted by I-cells in the small intestine and induces contraction of the gallbladder, relaxes the sphincter of Oddi, increases bile acid production in the liver, delays gastric emptying, and induces digestive enzyme production in the pancreas. Effects of CCK on the gastrointestinal tract.svg
Effects of cholecystokinin on the gastrointestinal tract. Cholecystokinin is secreted by I-cells in the small intestine and induces contraction of the gallbladder, relaxes the sphincter of Oddi, increases bile acid production in the liver, delays gastric emptying, and induces digestive enzyme production in the pancreas.

Satiety

As a peptide hormone, CCK mediates satiety by acting on the CCK receptors distributed widely throughout the central nervous system. The mechanism for hunger suppression is thought to be a decrease in the rate of gastric emptying. [28] CCK also has stimulatory effects on the vagus nerve, effects that can be inhibited by capsaicin. [29] The stimulatory effects of CCK oppose those of ghrelin, which has been shown to inhibit the vagus nerve. [30]

The effects of CCK vary between individuals. For example, in rats, CCK administration significantly reduces hunger in adult males, but is slightly less effective in younger subjects, and even slightly less effective in females. The hunger-suppressive effects of CCK also are reduced in obese rats. [31]

Neurological

CCK is found extensively throughout the central nervous system, with high concentrations found in the limbic system. [32] CCK is synthesized as a 115 amino acid preprohormone, that is then converted into multiple isoforms. [32] The predominant form of CCK in the central nervous system is the sulfated octapeptide, CCK-8S. [32]

Anxiogenic

In both humans and rodents, studies clearly indicate that elevated CCK levels causes increased anxiety. [26] The site of the anxiety-inducing effects of CCK seems to be central with specific targets being the basolateral amygdala, hippocampus, hypothalamus, periaqueductal grey, and cortical regions. [26] [33]

Panicogenic

The CCK tetrapeptide fragment CCK-4 (Trp-Met-Asp-Phe-NH2) reliably causes anxiety and panic attacks (panicogenic effect) when administered to humans and is commonly used in scientific research for this purpose of in order to test new anxiolytic drugs. [33] [34] Positron emission tomography visualization of regional cerebral blood flow in patients undergoing CCK-4 induced panic attacks show changes in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and cerebellar vermis. [32]

Hallucinogenic

Several studies have implicated CCK as a cause of visual hallucinations in Parkinson's disease. Mutations in CCK receptors in combination with mutated CCK genes potentiate this association. These studies also uncovered potential racial/ethnic differences in the distribution of mutated CCK genes. [20]

Interactions

CCK has been shown to interact with the cholecystokinin A receptor located mainly on pancreatic acinar cells and cholecystokinin B receptor mostly in the brain and stomach. CCKB receptor also binds gastrin, a gastrointestinal hormone involved in stimulating gastric acid release and growth of the gastric mucosa. [35] [36] [37] 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. [38] CCK has been shown to interact with orexin neurons, which control appetite and wakefulness (sleep). [39] CCK can have indirect effects on sleep regulation. [40]

CCK in the body cannot cross the blood–brain barrier, but certain parts of the hypothalamus and brainstem are not protected by the barrier.

See also

Related Research Articles

<span class="mw-page-title-main">Pancreas</span> Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.

<span class="mw-page-title-main">Duodenum</span> First section of the small intestine

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest part of the small intestine.

Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.

<span class="mw-page-title-main">Secretin</span> Hormone involved in stomach, pancreas and liver secretions

Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.

Chyme or chymus is the semi-fluid mass of partly digested food that is expelled by the stomach, through the pyloric valve, into the duodenum.

<span class="mw-page-title-main">Gastrin</span> Mammalian protein found in Homo sapiens

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

<span class="mw-page-title-main">Gastric acid</span> Digestive fluid formed in the stomach

Gastric acid or stomach acid is the acidic component – hydrochloric acid of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. With a pH of between one and three, gastric acid plays a key role in the digestion of proteins by activating digestive enzymes, which together break down the long chains of amino acids of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce mucus – a viscous barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to neutralize gastric acid passing into the digestive tract.

<span class="mw-page-title-main">Digestive enzyme</span> Class of enzymes

Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.

<span class="mw-page-title-main">Gastric inhibitory polypeptide</span> Mammalian protein found in Homo sapiens

Gastric inhibitory polypeptide(GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.

<span class="mw-page-title-main">Motilin</span> Protein family

Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.

<span class="mw-page-title-main">Gastrinoma</span> Medical condition

Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.

Pancreatic juice is a liquid secreted by the pancreas, which contains a number of digestive enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, nucleases and amylase. The pancreas is located in the visceral region, and is a major part of the digestive system required for proper digestion and subsequent assimilation of macronutrient substances required for living.

<span class="mw-page-title-main">Pancreatic polypeptide</span> Protein produced by the endocrine pancreas

Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It is a hormone and it regulates pancreatic secretion activities, and also impacts liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by certain endocrine tumours.

<span class="mw-page-title-main">Enteroendocrine cell</span> Cell that produces gastrointestinal hormones

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and excrete waste products. The GI tract is composed of the alimentary canal, that runs from the mouth to the anus, as well as the associated glands, chemicals, hormones, and enzymes that assist in digestion. The major processes that occur in the GI tract are: motility, secretion, regulation, digestion and circulation. The proper function and coordination of these processes are vital for maintaining good health by providing for the effective digestion and uptake of nutrients.

<span class="mw-page-title-main">Cholecystokinin A receptor</span> Protein-coding gene in the species Homo sapiens

The Cholecystokinin A receptor is a human protein, also known as CCKAR or CCK1, with CCK1 now being the IUPHAR-recommended name.

The nervous system, and endocrine system collaborate in the digestive system to control gastric secretions, and motility associated with the movement of food throughout the gastrointestinal tract, including peristalsis, and segmentation contractions.

The gastrin family of proteins is defined by the peptide hormones gastrin and cholecystokinin. Gastrin and cholecystokinin (CCK) are structurally and functionally related peptide hormones that serve as regulators of various digestive processes and feeding behaviors. Additional structurally related members of this family include the amphibian caerulein skin peptide, the cockroach leukosulphakinin I and II (LSK) peptides, Drosophila melanogaster putative CCK-homologs Drosulphakinins I and II, cionin, a chicken gastrin/cholecystokinin-like peptide and cionin, a neuropeptide from the protochordate Ciona intestinalis.

<span class="mw-page-title-main">Human digestive system</span> Digestive system in humans

The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion. Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has three stages: the cephalic phase, the gastric phase, and the intestinal phase.

<span class="mw-page-title-main">Monitor peptide</span> Peptide crucial to digestive regulation through the release of cholecystokinin (CCK)

Monitor peptide, also known as pancreatic secretory trypsin inhibitor I (PSTI-I) or pancreatic secretory trypsin inhibitor 61 (PSTI-61), is a peptide that plays an important role in the regulation of the digestive system, specifically the release of cholecystokinin (CCK).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000187094 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032532 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 4 Johnson LR (2013). Gastrointestinal Physiology (Eighth ed.). Philadelphia: Elsevier/Mosby. ISBN   978-0-323-10085-4.
  6. 1 2 Bowen R (28 January 2001). "Cholecystokinin". Colorado State University. Archived from the original on 17 March 2016. Retrieved 6 November 2015.
  7. ↑ Bernard C (1856). Leçons de physiologie expérimentale appliquée à la médecine (in French). Vol. 2. Paris, France: J.B. Baillière et fils. p. 430. From p. 430: "En effet, si l'on ouvre le duodenum sur un animal vivant et que l'on touche l'orifice du conduit cholédoque avec une baguette de verre imprégnée d'acide acétique faible, on voit immédiatement un flot de bile lancé dans l'intestin; ce qui ne se fait pas si, au lieu de toucher l'orifice du conduit cholédoque avec un liquide acide, on le touche avec un liquide lègérement alcalin, comme du carbonate de soude par example." (Indeed, if one opens the duodenum on a living animal and touches the orifice of the bile duct with a glass rod impregnated with weak acetic acid, one immediately sees a stream of bile squirted into the intestine; which is not done if, instead of touching the orifice of the bile duct with an acidic liquid, it is touched with a slightly alkaline liquid, such as sodium carbonate for example.)
  8. ↑ Rehfeld JF (March 2021). "Cholecystokinin and the hormone concept". Endocrine Connections. 10 (3): R139 –R150. doi:10.1530/EC-21-0025. PMC   8052576 . PMID   33640870.
  9. ↑ Wertheimer E (1903). "De l'action des acides et du chloral sur la sécrétion biliaire (d'après les expériences de M. Ch. Dubois)" [On the action of acids and chloral on bile secretion (according to the experiments of Mr. Charles Dubois)]. Compte Rendus Hebdomadaires des Séances et Mémoires de la Société Biologie (in French). 55: 286–287. From p. 287: "Ces expériences furent ensuite répétées après section préalable des pneumogastriques au cou et des sympathiques dans le thorax: cinq sur douze ont encore donné des résultats positifs." (These experiments [namely, introducing dilute acid into the duodenum in order to determine whether the acid then stimulated the secretion of bile] were then repeated after prior section [i.e., cutting] of the pneumogastric [i.e., vagus nerves] in the neck and the sympathetic [nerves] in the thorax: five out of twelve [experiments] again gave positive results.)
  10. ↑ Fleig C (1904). "Du mode d'action des excitants chimiques des glandes digestives" [On the mode of action of the chemical stimulants of the digestive glands]. Archives Internationales de Physiologie et de Biochimie (in French). 1: 286–346. From pp. 316-317: "Expérience. — Chien 13 k. chloralosé. On isole une anse de duodéno-jejunum, … C'est là pour le moment une question non résolue et qui ne m'a donné aucun résultat." (Experiment: A dog of 13 kg. was anaesthetized with chloral hydrate. One isolates a section of the duodenum-jejunum; one introduces into it a solution of 0.5% HCl, and one collects the venous blood from the section as usual. Infusion of the [venous] blood which is administered during 30 minutes (about 100 cc.) to a dog of 7 kg. having a canula in the bile duct and [having] the cystic duct bound. The flow of bile is increased to double ([see] fig. 44). But is this humoral action due to the same secretin that acts on the pancrease or [is it due to the action of] a special "crinine" [i.e., a hypothetical hormone that's involved in digestion, like Fleig's "sapocrinine" (see p. 293)] on the liver? For the moment it's an unresolved question and [one] that has given me no result.)
  11. ↑ Ivy AC, Oldberg E (October 1928). "A hormone mechanism for gall-bladder contraction and evacuation". American Journal of Physiology. 86 (3): 599–613. doi: 10.1152/ajplegacy.1928.86.3.599 .
  12. ↑ Harper AA, Raper HS (June 1943). "Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of the small intestine". The Journal of Physiology. 102 (1): 115–125. doi:10.1113/jphysiol.1943.sp004021. PMC   1393423 . PMID   16991584.
  13. ↑ Jorpes E, Mutt V (January–February 1966). "Cholecystokinin and pancreozymin, one single hormone?". Acta Physiologica Scandinavica. 66 (1): 196–202. doi:10.1111/j.1748-1716.1966.tb03185.x. PMID   5935672.
  14. ↑ Konturek PC, Konturek SJ (December 2003). "The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system" (PDF). Journal of Physiology and Pharmacology. 54 (Suppl 3): 83–98. PMID   15075466.
  15. ↑ Broden B (January 1958). "Experiments with cholecystokinin in cholecystography". Acta Radiologica. 49 (1): 25–30. doi: 10.3109/00016925809170975 . PMID   13508336.
  16. ↑ Mutt V, Jorpes JE (October 1968). "Structure of porcine cholecystokinin-pancreozymin. 1. Cleavage with thrombin and with trypsin". European Journal of Biochemistry. 6 (1): 156–162. doi: 10.1111/j.1432-1033.1968.tb00433.x . PMID   5725809.
  17. 1 2 3 4 Chaudhri O, Small C, Bloom S (July 2006). "Gastrointestinal hormones regulating appetite". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 361 (1471): 1187–1209. doi:10.1098/rstb.2006.1856. PMC   1642697 . PMID   16815798.
  18. ↑ Reeve JR, Eysselein VE, Rosenquist G, Zeeh J, Regner U, Ho FJ, et al. (May 1996). "Evidence that CCK-58 has structure that influences its biological activity". The American Journal of Physiology. 270 (5 Pt 1): G860 –G868. doi:10.1152/ajpgi.1996.270.5.G860. PMID   8967499.
  19. ↑ Agersnap M, Rehfeld JF (August 2014). "Measurement of nonsulfated cholecystokinins". Scandinavian Journal of Clinical and Laboratory Investigation. 74 (5): 424–431. doi:10.3109/00365513.2014.900695. PMID   24734780. S2CID   207421432.
  20. 1 2 Lenka A, Arumugham SS, Christopher R, Pal PK (May 2016). "Genetic substrates of psychosis in patients with Parkinson's disease: A critical review". Journal of the Neurological Sciences. 364: 33–41. doi:10.1016/j.jns.2016.03.005. PMID   27084212. S2CID   31298855.
  21. ↑ Ma Y, Giardino WJ (September 2022). "Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction". Addiction Neuroscience. 3: 100024. doi:10.1016/j.addicn.2022.100024. PMC   9380858 . PMID   35983578.
  22. ↑ Moran TH, Schwartz GJ (1994). "Neurobiology of cholecystokinin". Critical Reviews in Neurobiology. 9 (1): 1–28. PMID   8828002.
  23. ↑ Ma Y, Giardino WJ (September 2022). "Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction". Addiction Neuroscience. 3: 100024. doi:10.1016/j.addicn.2022.100024. PMC   9380858 . PMID   35983578.
  24. ↑ Rotzinger S, Vaccarino FJ (2003). "Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and reward-related behaviours in animal models". Journal of Psychiatry & Neuroscience. 28 (3): 171–181.
  25. ↑ Chey WY, Chang T (1 January 2001). "Neural hormonal regulation of exocrine pancreatic secretion". Pancreatology. 1 (4): 320–335. doi:10.1159/000055831. PMID   12120211. S2CID   22629842.
  26. 1 2 3 Skibicka KP, Dickson SL (December 2013). "Enteroendocrine hormones - central effects on behavior". Current Opinion in Pharmacology. 13 (6): 977–982. doi: 10.1016/j.coph.2013.09.004 . PMID   24091195.
  27. ↑ Liddle RA (September 1995). "Regulation of cholecystokinin secretion by intraluminal releasing factors". The American Journal of Physiology. 269 (3 Pt 1): G319 –G327. doi:10.1152/ajpgi.1995.269.3.G319. PMID   7573441.
  28. ↑ Shillabeer G, Davison JS (February 1987). "Proglumide, a cholecystokinin antagonist, increases gastric emptying in rats". The American Journal of Physiology. 252 (2 Pt 2): R353 –R360. doi:10.1152/ajpregu.1987.252.2.R353. PMID   3812772.
  29. ↑ Holzer P (July 1998). "Neural injury, repair, and adaptation in the GI tract. II. The elusive action of capsaicin on the vagus nerve". The American Journal of Physiology. 275 (1): G8-13. doi:10.1152/ajpgi.1998.275.1.G8. PMID   9655678.
  30. ↑ Kobelt P, Tebbe JJ, Tjandra I, Stengel A, Bae HG, Andresen V, et al. (March 2005). "CCK inhibits the orexigenic effect of peripheral ghrelin". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 288 (3): R751 –R758. doi:10.1152/ajpregu.00094.2004. PMID   15550621.
  31. ↑ Fink H, Rex A, Voits M, Voigt JP (November 1998). "Major biological actions of CCK--a critical evaluation of research findings". Experimental Brain Research. 123 (1–2): 77–83. doi:10.1007/s002210050546. PMID   9835394. S2CID   11251325.
  32. 1 2 3 4 Bowers ME, Choi DC, Ressler KJ (December 2012). "Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y". Physiology & Behavior. 107 (5): 699–710. doi:10.1016/j.physbeh.2012.03.004. PMC   3532931 . PMID   22429904.
  33. 1 2 Zwanzger P, Domschke K, Bradwejn J (September 2012). "Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin". Depression and Anxiety. 29 (9): 762–774. doi: 10.1002/da.21919 . PMID   22553078. S2CID   24581213.
  34. ↑ Bradwejn J (July 1993). "Neurobiological investigations into the role of cholecystokinin in panic disorder". Journal of Psychiatry & Neuroscience. 18 (4): 178–188. PMC   1188527 . PMID   8104032.
  35. ↑ Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (January 2005). "Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy". The Journal of Biological Chemistry. 280 (2): 1044–1050. doi: 10.1074/jbc.M409480200 . PMID   15520004.
  36. ↑ Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, et al. (March 2004). "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". Journal of Nuclear Medicine. 45 (3): 485–494. PMID   15001692. ProQuest   219229095.
  37. ↑ Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, et al. (May 2003). "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". Molecular Pharmacology. 63 (5): 973–982. doi:10.1124/mol.63.5.973. PMID   12695525. S2CID   38395309.
  38. ↑ Gurda GT, Guo L, Lee SH, Molkentin JD, Williams JA (January 2008). "Cholecystokinin activates pancreatic calcineurin-NFAT signaling in vitro and in vivo". Molecular Biology of the Cell. 19 (1): 198–206. doi:10.1091/mbc.E07-05-0430. PMC   2174201 . PMID   17978097.
  39. ↑ Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, et al. (August 2005). "Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor". The Journal of Neuroscience. 25 (32): 7459–7469. doi: 10.1523/JNEUROSCI.1193-05.2005 . PMC   6725310 . PMID   16093397.
  40. ↑ Kapas L (2010). Metabolic signals in sleep regulation: the role of cholecystokinin (PDF). The Journal of Neuroscience (PhD thesis). University of Szeged.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.