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the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system
the 16th letter of the Roman alphabet (同)p
a river in western Thailand; a major tributary of the Chao Phraya (同)Ping River

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carbonの化学記号
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/08 11:46:53」(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[edit source | edit]

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.^[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.

Functions[edit source | edit]

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 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. Trypsin, a protease released by pancreatic acinar cells hydrolyzes CCK-releasing peptide and monitor peptide effectively 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 micelles that emulsify fats, aiding in their digestion and absorption.

Neurobiology[edit source | edit]

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

CCK also has stimulatory effects on the vagus nerve, effects that can be inhibited by capsaicin.^[6] The stimulatory effects of CCK oppose those of ghrelin, which has been shown to inhibit the vagus nerve.^[7] 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.^[8]

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.^[9]

Interactions[edit source | edit]

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.^[10]^[11]^[12]

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.^[13]

Cholecystokinin has been shown to interact with orexin neurons which control appetite and wakefulness (sleep).^[14] Cholecystokinin can have indirect effects on sleep regulation.^[15]

Cholecystokinin in the body cannot cross the blood brain barrier, but certain parts of the hypothalamus and brainstem aren't protected by the barrier.

In the hypothalamus, CCK8 injection excites CRF neurosecretory neurons in par ventricular nucleus that is different cell responsive to pain stimulation:They show slow a 1 sec-hyperpolarizaiton with subsequent long (30min) depolarization to CCK8 injection (psychological stress), whereas tail pinch (physical stress), transient excitation. Consistently, in the cerebellum, Golgi cells express c-fos mRNA to CCK8 injection, whereas granule cells express junD mRNA to capsaicin injection to the limb skin. Thus, psychological and physical stress excite different neural path.

References[edit source | edit]

^ 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 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.
^ 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.
^ 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 (PhD thesis). University of Szeged. http://www.phd.szote.u-szeged.hu/Elmeleti_DI/Disszertaciok/2010/de_Levente_Kapas.pdf.

External links[edit source | edit]

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. 膵外分泌機能検査 pancreatic exocrine function tests
3. 成人における胆嚢機能障害 functional gallbladder disorder in adults
4. Pathophysiology of short bowel syndrome
5. ガストリンの生理学 physiology of gastrin

English Journal

Insulin versus glucagon crosstalk: central plus peripheral mechanisms.

Lechin F1, Dijs Bv, Pardey-Maldonado B.
American journal of therapeutics.Am J Ther.2013 Jul-Aug;20(4):349-62. doi: 10.1097/MJT.0b013e318235f295.
Plasma glucose level depends on the peripheral intra-islet crosstalk between A cells (glucagon) + B-cells (insulin) and D-cells (somatostatin). Gastrointestinal hormones (secretin, CCK-PZ, gastrin, and serotonin) modulate the glucose- and amino acids-induced secretions of insulin and glucagon, respe
PMID 23838633

[Cholecystokinin-pancreozymin (CCK-PZ)].

Sakaguchi H1, Iwata Y, Kobayashi K, Arakawa T.
Nihon rinsho. Japanese journal of clinical medicine.Nihon Rinsho.2010 Jul;68 Suppl 7:544-6.
PMID 20960826

[Cholecystokinin-pancreozymin (CCK-PZ)].

Sakaguchi H1, Iwata Y, Kobayashi K, Arakawa T.
Nihon rinsho. Japanese journal of clinical medicine.Nihon Rinsho.2005 Aug;63 Suppl 8:505-7.
PMID 16149563

Japanese Journal

コレシストキニン・パンクレオザイミン(CCK-PZ) (広範囲血液・尿化学検査免疫学的検査(第7版・4)その数値をどう読むか) -- (内分泌学的検査膵・消化管関係)

坂口浩樹,岩田康博,小林絢三 [他]
日本臨床 68(-) (982), 544-546, 2010-07
NAID 40017200805

各種消化管ホルモンおよび合成トリプシンインヒビターの切除膵再生に及ぼす影響の実験的研究

常見幸三,田中龍彦,山本正博,斉藤洋一
神戸大学医学部紀要 54(2/3/4), 43-50, 1994-03
… その結果、CCK-PZのanalogueであるセルレイン投与で残膵重量,残膵総アミラーゼ量,総蛋白量,総DNA量の増加を認めた。 … また,CAMOSTAT経口投与時の血中CCK-PZ濃度は,CAMOSTAT単回投与では2時間後に前値の約7倍まで,また,連続投与では3日目に約5倍まで上昇し,その後も高値を維持した。 …
NAID 110001179301

Related Pictures

★リンクテーブル★

リンク元	「コレシストキニン」
関連記事	「C」「CC」「P」「CCK」

「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;
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; • negative regulation of appetite; • positive regulation of protein oligomerization; • eating behavior; • positive regulation of apoptotic process; • 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
	This box: view; talk; edit;

　　[★]

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

「C」

　　[★]

炭素 carbon
シトシン cytosine
システイン cysteine
シチジン
セルシウス度摂氏 degrees Celsius degree C
産婦人科領域で「子宮外頚子宮外頚部 exocervix」を表現するための略語

「CC」

　　[★]

「P」

　　[★]

「CCK」

　　[★] コレシストキニン cholecystokinin

[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 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.

[pmid9855480-4] 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.

[pmid3812772-5] 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.

[pmid9655678-6] 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.

[pmid15550621-7] 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.

[pmid8104032-8] 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.

[pmid9835394-9] 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.

[pmid15520004-10] 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.

[pmid15001692-11] 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.

[pmid12695525-12] 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.

[pmid17978097-13] 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.

[pmid16093397-14] 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.

[15] Kapas, Levente (2010). Metabolic signals in sleep regulation: the role of cholecystokinin (PhD thesis). University of Szeged. http://www.phd.szote.u-szeged.hu/Elmeleti_DI/Disszertaciok/2010/de_Levente_Kapas.pdf.

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案内

CCK-PZ