WordNet

a gastrointestinal hormone that stimulates the secretion of pancreatic enzymes and the contraction and emptying of the gall bladder; its release is stimulated by the presence of fatty acids and amino acids in the small intestine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/26 11:19:04」(JST)

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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 synthesized 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, CCK22 and CCK8. CCK58 assumes a helix-turn-helix configuration.^[3] 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. Most CCK peptides have a sulfate-group attached to the tyrosine in position 7 in the C-terminus. 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.^[4]

Functions

CCK mediates a number of physiological processes, including digestion and satiety. It is released by I cells located in the mucosal epithelium of the small intestine (mostly in the duodenum and jejunum), neurons of the enteric nervous system, and neurons in the brain. Release of CCK is stimulated by monitor peptide released by pancreatic acinar cells as well as CCK-releasing protein, a paracrine factor secreted by enterocytes in the gastrointestinal mucosa. In addition, release of acetylcholine by the parasympathetic nerve fibers of the vagus nerve also stimulate its secretion. The presence of fatty acids and/or certain amino acids in the chyme entering the duodenum is the greatest stimulator of CCK release.

CCK mediates digestion in the small intestine by inhibiting gastric emptying and decreasing gastric acid secretion. It stimulates the acinar cells of the pancreas to release digestive enzymes 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 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.

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 lipids, micelles that emulsify fats, aiding in their digestion and absorption.

Neurobiology

As a peptide hormone, 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. CCK-4 is routinely used to induce anxiety in humans though certainly different forms of CCK are being shown to have highly variable effects.^[5] The mechanism for this hunger suppression is thought to be a decrease in the rate of gastric emptying.^[6]

CCK also has stimulatory effects on the vagus nerve, effects that can be inhibited by capsaicin.^[7] The stimulatory effects of CCK oppose those of ghrelin, which has been shown to inhibit the vagus nerve.^[8] 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.^[9] One study shows that visual hallucinations in Parkinson's disease are associated with cholecystokinin −45C>T polymorphism, and this association is still observed in the presence of the cholecystokinin-A receptor TC/CC genotype, indicating a possible interaction of these two genes in the visual hallucinogenesis in Parkinson's disease.^[10]

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.^[11]

Interactions

Cholecystokinin 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. CCK_B receptor also binds gastrin, a gastrointestinal hormone involved in stimulating gastric acid release and growth of the gastric mucosa.^[12]^[13]^[14]

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.^[15]

Cholecystokinin has been shown to interact with orexin neurons, which control appetite and wakefulness (sleep).^[16] Cholecystokinin can have indirect effects on sleep regulation.^[17]

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

References

^ 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:10.1097/00000539-200007000-00021. PMID 10866896.
^ 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:10.1254/jphs.FP0070475. PMID 17558184.
^ Reeve JR, Eysselein VE, Rosenquist G, Zeeh J, Regner U, Ho FJ, Chew P, Davis MT, Lee TD, Shively JE, Brazer SR, Liddle RA (1996). "Evidence that CCK-58 has structure that influences its biological activity". Am. J. Physiol. 270 (5 Pt 1): G860–8. PMID 8967499.
^ Agersnap M, Rehfeld JF (2014). "Measurement of nonsulfated cholecystokinins". Scand. J. Clin. Lab. Invest. 74 (5): 424–31. doi:10.3109/00365513.2014.900695. PMID 24734780.
^ 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:10.1016/S0031-9384(98)00169-3. PMID 9855480.
^ 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.
^ Holzer P (July 1998). "Neural injury, repair, and adaptation in the GI tract. II. The elusive action of capsaicin on the vagus nerve". Am. J. Physiol. 275 (1 Pt 1): G8–13. PMID 9655678.
^ Kobelt P, Tebbe JJ, Tjandra I, Stengel A, Bae HG, Andresen V, van der Voort IR, Veh RW, Werner CR, Klapp BF, Wiedenmann B, Wang L, Taché Y, Mönnikes H (March 2005). "CCK inhibits the orexigenic effect of peripheral ghrelin". Am. J. Physiol. Regul. Integr. Comp. Physiol. 288 (3): R751–8. doi:10.1152/ajpregu.00094.2004. PMID 15550621.
^ Bradwejn J (July 1993). "Neurobiological investigations into the role of cholecystokinin in panic disorder". J Psychiatry Neurosci 18 (4): 178–88. PMC 1188527. PMID 8104032.
^ Wang J, Si YM, Liu ZL, Yu L. (June 2003). "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease.". Pharmacogenetics 13 (6): 365–9. doi:10.1097/00008571-200306000-00008. PMID 12777967.
^ 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:10.1007/s002210050546. PMID 9835394.
^ 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". J. Biol. Chem. 280 (2): 1044–50. doi:10.1074/jbc.M409480200. PMID 15520004.
^ Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (March 2004). "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". J. Nucl. Med. 45 (3): 485–94. PMID 15001692.
^ Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, Escrieut C, Pradayrol L, Fourmy D, Silvente-Poirot S (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". Mol. Pharmacol. 63 (5): 973–82. doi:10.1124/mol.63.5.973. PMID 12695525.
^ Gurda GT, Guo L, Lee SH, Molkentin JD, Williams JA (January 2008). "Cholecystokinin activates pancreatic calcineurin-NFAT signaling in vitro and in vivo". Mol. Biol. Cell 19 (1): 198–206. doi:10.1091/mbc.E07-05-0430. PMC 2174201. PMID 17978097.
^ Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, Takahashi S, Goto K, Sakurai T (August 2005). "Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor". J. Neurosci. 25 (32): 7459–69. doi:10.1523/JNEUROSCI.1193-05.2005. PMID 16093397.
^ Kapas, Levente (2010). Metabolic signals in sleep regulation: the role of cholecystokinin (PDF). The Journal of Neuroscience (PhD thesis) (University of Szeged).

External links

Cholecystokinin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. コレシストキニンの生理学 physiology of cholecystokinin
2. 成人における胆嚢機能障害 functional gallbladder disorder in adults
3. Exocrine pancreatic insufficiency
4. オッディ括約筋機能不全の臨床症状よび診断 clinical manifestations and diagnosis of sphincter of oddi dysfunction
5. ガストリンの生理学 physiology of gastrin

English Journal

Dual-agonist occupancy of orexin receptor 1 and cholecystokinin A receptor heterodimers decreases G-protein-dependent signaling and migration in the human colon cancer cell line HT-29.

Bai B1, Chen X2, Zhang R1, Wang X1, Jiang Y1, Li D1, Wang Z1, Chen J3.
Biochimica et biophysica acta.Biochim Biophys Acta.2017 Jul;1864(7):1153-1164. doi: 10.1016/j.bbamcr.2017.03.003. Epub 2017 Mar 10.
PMID 28288880

Effects of fasting and refeeding on the digestive tract of zebrafish (Danio rerio) fed with Spirulina (Arthrospira platensis), a high protein feed source.

Lo Cascio P1, Calabrò C1, Bertuccio C1, Paterniti I1, Palombieri D1, Calò M2, Albergamo A3,4, Salvo A3,4, Gabriella Denaro M1.
Natural product research.Nat Prod Res.2017 Jul;31(13):1478-1485. doi: 10.1080/14786419.2016.1274893. Epub 2017 Jan 3.
PMID 28044454

Appetite suppressing effect of Spinacia oleracea in rats: Involvement of the short term satiety signal cholecystokinin.

Panda V1, Shinde P2.
Appetite.Appetite.2017 Jun 1;113:224-230. doi: 10.1016/j.appet.2017.02.030. Epub 2017 Feb 24.
PMID 28238891

Characterization of appetite-regulating factors in platyfish, Xiphophorus maculatus (Cyprinodontiformes Poeciliidae).

Pitts PM1, Volkoff H2.
Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.Comp Biochem Physiol A Mol Integr Physiol.2017 Jun;208:80-88. doi: 10.1016/j.cbpa.2017.03.018. Epub 2017 Apr 3.
PMID 28377124

Japanese Journal

発育関連遺伝子を指標とした地頭鶏の選抜試験(第1報)

津曲明美,稲井耕次,高橋秀彰
宮崎県畜産試験場試験研究報告 (26), 111-113, 2014-12
NAID 40020401699

コレシストキニンA受容体遺伝子g.420 C>A一塩基多型は比内鶏の発育を改善する

力丸宗弘,武田尚人,大久保武 [他]
日本家禽学会誌 52(J2), J43-48, 2014-10
NAID 40020246829

Yellowtail neuropeptide Y : molecular cloning, tissue distribution, and response to fasting

Hosomi Noriko,Furutani Takahiro,Takahashi Noriyuki [他]
Fisheries science 80(3), 483-492, 2014-05
NAID 40020063514

平成24年度岡山医学会賞総合研究奨励賞(結城賞) 糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する

宮本聡,四方賢一,宮坂京子 [他],岡田震一,佐々木基史,小寺亮,廣田大昌,梶谷展生,高塚哲全,片岡仁美,西下伸吾,堀口千景,船越顕博,西森久和,内田治仁,小川大輔,槇野博史
岡山医学会雑誌 126(1), 1-6, 2014-04
NAID 120005425651

「コレシストキニン」

Cholecystokinin
Identifiers
Symbols	CCK ; MGC117187
External IDs	OMIM: 118440 MGI: 88297 HomoloGene: 583 ChEMBL: 1649050 GeneCards: CCK Gene
Gene ontology
Molecular function	• hormone activity; • neuropeptide hormone activity; • protein binding;
Cellular component	• extracellular region; • extracellular space; • axon; • dendrite; • axon initial segment; • terminal bouton; • axon hillock; • perikaryon;
Biological process	• behavioral fear response; • neuron migration; • release of cytochrome c from mitochondria; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • signal transduction; • protein kinase C-activating G-protein coupled receptor signaling pathway; • axonogenesis; • positive regulation of cell proliferation; • positive regulation of glutamate secretion; • negative regulation of appetite; • positive regulation of protein oligomerization; • eating behavior; • positive regulation of peptidyl-tyrosine phosphorylation; • positive regulation of mitochondrial depolarization; • regulation of sensory perception of pain;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: cholecystokinin, CCK
同: コレシストキニン・パンクレオザイミン cholecystokinin pancreozymin CCK-PZ; パンクレオザイミン pancreozymin
関: 消化管ホルモン、胆嚢収縮物質

[show details]

コレシストキニン : 約 25,900 件
パンクレオザイミン : 約 4,080 件

まとめ

小腸内タンパク質分解産物、酸、脂肪酸、アルコールが刺激となって、小腸のI細胞から分泌され、消化酵素に富む膵液を分泌させる。またオッディ括約筋を弛緩させ、胆嚢を収縮させて胆汁の分泌を促す。

分泌部位と細胞

十二指腸、空腸のI細胞

作用

胃

↓：胃排出(First Aid step 1 p.269)
↑：胃酸分泌(CBT QB vol2 p.295)

胆嚢

↑：胆嚢を収縮 (SP.706)
↑：胆嚢外分泌腺増加

胆膵管

↓：胆膵管膨大部括約筋(オッディ括約筋)を弛緩 (SP.706)

膵

↑：膵液分泌(First Aid step 1 p.269)
↑：外分泌腺増加

調節 (First Aid step 1 p.269)

↑

脂肪酸、アミノ酸

↓

セクレチン
胃のpH<1.5

臨床関連

胆石症

脂肪摂取→CCK↑→胆汁↑→いたいっ

「CCK」

　　[★] コレシストキニン cholecystokinin

「cholecystokinin receptor」

　　[★]

コレシストキニン受容体、コレシストキニンレセプター

関: CCK receptor

「cholecystokinin pancreozymin」

　　[★] コレシストキニン。コレシストキニン・パンクレオザイミン

「cholecystokinin 8」

　　[★]

コレシストキニン-8

関: CCK-8、cholecystokinin octapeptide

[pmid10866896-1] 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:10.1097/00000539-200007000-00021. PMID 10866896.

[pmid17558184-2] 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:10.1254/jphs.FP0070475. PMID 17558184.

[pmid8967499-3] Reeve JR, Eysselein VE, Rosenquist G, Zeeh J, Regner U, Ho FJ, Chew P, Davis MT, Lee TD, Shively JE, Brazer SR, Liddle RA (1996). "Evidence that CCK-58 has structure that influences its biological activity". Am. J. Physiol. 270 (5 Pt 1): G860–8. PMID 8967499.

[PMID_24734780-4] Agersnap M, Rehfeld JF (2014). "Measurement of nonsulfated cholecystokinins". Scand. J. Clin. Lab. Invest. 74 (5): 424–31. doi:10.3109/00365513.2014.900695. PMID 24734780.

[pmid9855480-5] 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:10.1016/S0031-9384(98)00169-3. PMID 9855480.

[pmid3812772-6] 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.

[pmid9655678-7] Holzer P (July 1998). "Neural injury, repair, and adaptation in the GI tract. II. The elusive action of capsaicin on the vagus nerve". Am. J. Physiol. 275 (1 Pt 1): G8–13. PMID 9655678.

[pmid15550621-8] Kobelt P, Tebbe JJ, Tjandra I, Stengel A, Bae HG, Andresen V, van der Voort IR, Veh RW, Werner CR, Klapp BF, Wiedenmann B, Wang L, Taché Y, Mönnikes H (March 2005). "CCK inhibits the orexigenic effect of peripheral ghrelin". Am. J. Physiol. Regul. Integr. Comp. Physiol. 288 (3): R751–8. doi:10.1152/ajpregu.00094.2004. PMID 15550621.

[pmid8104032-9] Bradwejn J (July 1993). "Neurobiological investigations into the role of cholecystokinin in panic disorder". J Psychiatry Neurosci 18 (4): 178–88. PMC 1188527. PMID 8104032.

[pmid12777967-10] Wang J, Si YM, Liu ZL, Yu L. (June 2003). "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease.". Pharmacogenetics 13 (6): 365–9. doi:10.1097/00008571-200306000-00008. PMID 12777967.

[pmid9835394-11] 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:10.1007/s002210050546. PMID 9835394.

[pmid15520004-12] 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". J. Biol. Chem. 280 (2): 1044–50. doi:10.1074/jbc.M409480200. PMID 15520004.

[pmid15001692-13] Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (March 2004). "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". J. Nucl. Med. 45 (3): 485–94. PMID 15001692.

[pmid12695525-14] Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, Escrieut C, Pradayrol L, Fourmy D, Silvente-Poirot S (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". Mol. Pharmacol. 63 (5): 973–82. doi:10.1124/mol.63.5.973. PMID 12695525.

[pmid17978097-15] Gurda GT, Guo L, Lee SH, Molkentin JD, Williams JA (January 2008). "Cholecystokinin activates pancreatic calcineurin-NFAT signaling in vitro and in vivo". Mol. Biol. Cell 19 (1): 198–206. doi:10.1091/mbc.E07-05-0430. PMC 2174201. PMID 17978097.

[pmid16093397-16] Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, Takahashi S, Goto K, Sakurai T (August 2005). "Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor". J. Neurosci. 25 (32): 7459–69. doi:10.1523/JNEUROSCI.1193-05.2005. PMID 16093397.

[17] Kapas, Levente (2010). Metabolic signals in sleep regulation: the role of cholecystokinin (PDF). The Journal of Neuroscience (PhD thesis) (University of Szeged).

リンク元	「コレシストキニン」「CCK」
拡張検索	「cholecystokinin receptor」「cholecystokinin pancreozymin」「cholecystokinin 8」

匿名

検索

案内

案内

cholecystokinin