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Gene Review

CCK  -  cholecystokinin

Homo sapiens

Synonyms: Cholecystokinin
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Disease relevance of CCK


Psychiatry related information on CCK


High impact information on CCK


Chemical compound and disease context of CCK


Biological context of CCK


Anatomical context of CCK


Associations of CCK with chemical compounds

  • In loxiglumide-treated subjects there was a 4-5-fold elevation in plasma CCK levels [7].
  • METHODS: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol [25].
  • The response to CCK was inhibited in a competitive manner by the addition of the benzodiazepine analog, MK-329 [26].
  • CCK treatment induced an increase of intracellular cGMP concentrations, but concomitant addition of LY 83583 virtually suppressed this increase [1].
  • Identification of the two amino acids was achieved by dynamics-based docking of CCK in a refined three-dimensional model of CCK-AR using, as constraints, previous results that demonstrated that Trp-39/Gln-40 and Met-195/Arg-197 interact with the N terminus and the sulfated tyrosine of CCK, respectively [27].
  • EWS/FLI1 knockdown in A673 and SK-PN-DW Ewing cells using two different doxycycline-inducible EWS/FLI1-specific shRNA vectors down-regulated CCK mRNA expression and diminished the levels of secreted CCK, showing that CCK is a EWS/FLI1 specific target gene in Ewing cells [28].
  • Partial intraclass correlation showed an independent correlation of plasma CCK with free fatty acids (r(ic) = -0.377, P < 0.001) but not with serum insulin (r(ic) = 0.077, P = 0.32) [29].

Physical interactions of CCK


Regulatory relationships of CCK


Other interactions of CCK

  • No significant intergroup differences were noted in postprandial levels of Nt and CCK [39].
  • These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle [24].
  • Issues considered include, the effects of systemic injection of CCK on consummatory and operant feeding, the role of the vagus nerve, the effects of CCKB receptor antagonists, and the neuroendocrine responses to exogenous CCK [40].
  • CCK-8 markedly stimulated colony formation in GLC19 cells in a dose-dependent manner in the nanomolar range, whereas over the same concentration range, gastrin had no effect on clonal growth [35].
  • Cortical Sources of CRF, NKB, and CCK and Their Effects on Pyramidal Cells in the Neocortex [41].

Analytical, diagnostic and therapeutic context of CCK

  • METHODS: CCK receptors were localized by in vitro receptor autoradiography with 125I-[Leu15]gastrin-I and 125I-[D-Tyr-Gly, Nle(28,31)]-CCK 26-33 in stomach and gallbladder [42].
  • Our genetic dissection of the CCK system thus far suggests that the CCK-B receptor gene variation may contribute to the neurobiology of panic disorder [8].
  • We determined whether cortical levels of CCK might be similarly affected in AD by dissecting postmortem brain samples from 14 histologically confirmed cases of AD and 17 age-matched controls and measuring CCK and somatostatin by radioimmunoassay [43].
  • However, future investigations using CCK receptor antagonists with better pharmacokinetic characteristics and animal models other than those validated with the classical anxiolytics benzodiazepines may permit a more precise evaluation of the potential of these compounds as anti-anxiety agents [9].
  • In the present study we have evaluated gastrin and CCK gene expression in a group of primary human tumors, including neuronal, renal, and myogenic stem cell tumors, using in situ hybridization techniques [2].


  1. Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Cordelier, P., Estève, J.P., Bousquet, C., Delesque, N., O'Carroll, A.M., Schally, A.V., Vaysse, N., Susini, C., Buscail, L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  2. High gastrin and cholecystokinin (CCK) gene expression in human neuronal, renal, and myogenic stem cell tumors: comparison with CCK-A and CCK-B receptor contents. Schaer, J.C., Reubi, J.C. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  3. Immunohistochemical localization of CCK1 cholecystokinin receptors in normal and neoplastic human tissues. Schulz, S., Röcken, C., Mawrin, C., Schulz, S. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  4. Genetic, pharmacological and functional analysis of cholecystokinin-1 and cholecystokinin-2 receptor polymorphism in type 2 diabetes and obese patients. Marchal-Victorion, S., Vionnet, N., Escrieut, C., Dematos, F., Dina, C., Dufresne, M., Vaysse, N., Pradayrol, L., Froguel, P., Fourmy, D. Pharmacogenetics (2002) [Pubmed]
  5. Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: synergism with pharmacological levels of melatonin. González-Puga, C., García-Navarro, A., Escames, G., León, J., López-Cantarero, M., Ros, E., Acuña-Castroviejo, D. J. Pineal Res. (2005) [Pubmed]
  6. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Nguyen, N.Q., Fraser, R.J., Chapman, M.J., Bryant, L.K., Holloway, R.H., Vozzo, R., Wishart, J., Feinle-Bisset, C., Horowitz, M. Crit. Care Med. (2007) [Pubmed]
  7. Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans. Drewe, J., Gadient, A., Rovati, L.C., Beglinger, C. Gastroenterology (1992) [Pubmed]
  8. Investigation of cholecystokinin system genes in panic disorder. Kennedy, J.L., Bradwejn, J., Koszycki, D., King, N., Crowe, R., Vincent, J., Fourie, O. Mol. Psychiatry (1999) [Pubmed]
  9. Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders? Griebel, G. Pharmacol. Ther. (1999) [Pubmed]
  10. Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system. Goldman, J.G., Goetz, C.G., Berry-Kravis, E., Leurgans, S., Zhou, L. Arch. Neurol. (2004) [Pubmed]
  11. The influence of cholecystokinin on gastric myoelectrical activity in duodenal ulcer following Helicobacter pylori eradication--an electrogastrographic study. Budzyński, A., Bobrzyński, A., Lorens, K., Konturek, P.C., Thor, P., Konturek, S.J. J. Physiol. Pharmacol. (2002) [Pubmed]
  12. Cholecystokinin and gastrin receptors. Dufresne, M., Seva, C., Fourmy, D. Physiol. Rev. (2006) [Pubmed]
  13. Role of cholecystokinin and opioid peptides in control of food intake. Baile, C.A., McLaughlin, C.L., Della-Fera, M.A. Physiol. Rev. (1986) [Pubmed]
  14. Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. Creutzfeldt, W. N. Engl. J. Med. (2001) [Pubmed]
  15. Impaired cholecystokinin secretion in bulimia nervosa. Geracioti, T.D., Liddle, R.A. N. Engl. J. Med. (1988) [Pubmed]
  16. Gastro-intestinal and neurohormonal peptides in the alimentary tract and cerebral complex of Ciona intestinalis (Ascidiaceae). Fritsch, H.A., Van Noorden, S., Pearse, A.G. Cell Tissue Res. (1982) [Pubmed]
  17. Influence of cholecystitis state on pharmacological response to cholecystokinin of isolated human gallbladder with gallstones. Martínez-Cuesta, M.A., Moreno, L., Morillas, J., Ponce, J., Esplugues, J.V. Dig. Dis. Sci. (2003) [Pubmed]
  18. Meningiomas expressing and responding to cholecystokinin (CCK). Oikonomou, E., Machado, A.L., Buchfelder, M., Adams, E.F. J. Neurooncol. (2005) [Pubmed]
  19. Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. Bajorek, J.G., Lee, R.J., Lomax, P. Advances in neurology. (1986) [Pubmed]
  20. The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs. Song, I., Brown, D.R., Wiltshire, R.N., Gantz, I., Trent, J.M., Yamada, T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. Molecular cloning of the human cholecystokinin gene by use of a synthetic probe containing deoxyinosine. Takahashi, Y., Kato, K., Hayashizaki, Y., Wakabayashi, T., Ohtsuka, E., Matsuki, S., Ikehara, M., Matsubara, K. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  22. Cholecystokinin receptors in human pancreas and gallbladder muscle: a comparative study. Tang, C., Biemond, I., Lamers, C.B. Gastroenterology (1996) [Pubmed]
  23. Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans. Schmidt, W.E., Schenk, S., Nustede, R., Holst, J.J., Fölsch, U.R., Creutzfeldt, W. Gastroenterology (1994) [Pubmed]
  24. Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors. Clavé, P., González, A., Moreno, A., López, R., Farré, A., Cussó, X., D'Amato, M., Azpiroz, F., Lluís, F. Gastroenterology (1998) [Pubmed]
  25. Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin. Ji, B., Bi, Y., Simeone, D., Mortensen, R.M., Logsdon, C.D. Gastroenterology (2001) [Pubmed]
  26. Effect of cholecystokinin and secretin on somatostatin release from cultured antral cells. Buchan, A.M., Meloche, R.M., Kwok, Y.N., Kofod, H. Gastroenterology (1993) [Pubmed]
  27. Arginine 336 and asparagine 333 of the human cholecystokinin-A receptor binding site interact with the penultimate aspartic acid and the C-terminal amide of cholecystokinin. Gigoux, V., Escrieut, C., Fehrentz, J.A., Poirot, S., Maigret, B., Moroder, L., Gully, D., Martinez, J., Vaysse, N., Fourmy, D. J. Biol. Chem. (1999) [Pubmed]
  28. Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth. Carrillo, J., García-Aragoncillo, E., Azorín, D., Agra, N., Sastre, A., González-Mediero, I., García-Miguel, P., Pestaña, A., Gallego, S., Segura, D., Alonso, J. Clin. Cancer Res. (2007) [Pubmed]
  29. Effects of euglycemic hyperinsulinemia and lipid infusion on circulating cholecystokinin. Weickert, M.O., Möhlig, M., Spranger, J., Schöfl, C., Loeffelholz, C.V., Riepl, R.L., Otto, B., Pfeiffer, A.F. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  30. Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin. Kennedy, K., Gigoux, V., Escrieut, C., Maigret, B., Martinez, J., Moroder, L., Fréhel, D., Gully, D., Vaysse, N., Fourmy, D. J. Biol. Chem. (1997) [Pubmed]
  31. Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor. Giragossian, C., Mierke, D.F. Biochemistry (2002) [Pubmed]
  32. G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors: an exemplary family. Wank, S.A. Am. J. Physiol. (1998) [Pubmed]
  33. Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade. Katschinski, M., Steinicke, C., Reinshagen, M., Dahmen, G., Beglinger, C., Arnold, R., Adler, G. Eur. J. Clin. Invest. (1995) [Pubmed]
  34. Serotonin and gastrin/cholecystokinin-like immunoreactive neurons in the larval retrocerebral complex of the blowfly Calliphora erythrocephala. Cantera, R. Cell Tissue Res. (1988) [Pubmed]
  35. CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth. Sethi, T., Herget, T., Wu, S.V., Walsh, J.H., Rozengurt, E. Cancer Res. (1993) [Pubmed]
  36. Cholecystokinin (CCK) stimulates aldosterone secretion from human adrenocortical cells via CCK2 receptors coupled to the adenylate cyclase/protein kinase A signaling cascade. Mazzocchi, G., Malendowicz, L.K., Aragona, F., Spinazzi, R., Nussdorfer, G.G. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  37. The cholecystokinin gene is abundantly co-expressed with gastrin-releasing peptide, enkephalin and neuropeptide Y genes in a clonal human neuroepithelioma cell line. Verbeeck, M.A., Burbach, J.P. FEBS Lett. (1990) [Pubmed]
  38. Closing the gastrin loop in pancreatic carcinoma: coexpression of gastrin and its receptor in solid human pancreatic adenocarcinoma. Goetze, J.P., Nielsen, F.C., Burcharth, F., Rehfeld, J.F. Cancer (2000) [Pubmed]
  39. Postprandial levels of prolactin and gut hormones in breast cancer patients: association with stage of disease, but not dietary fat. Goettler, D.M., Levin, L., Chey, W.Y. J. Natl. Cancer Inst. (1990) [Pubmed]
  40. Food for thought: a critique on the hypothesis that endogenous cholecystokinin acts as a physiological satiety factor. Baldwin, B.A., Parrott, R.F., Ebenezer, I.S. Prog. Neurobiol. (1998) [Pubmed]
  41. Cortical Sources of CRF, NKB, and CCK and Their Effects on Pyramidal Cells in the Neocortex. Gallopin, T., Geoffroy, H., Rossier, J., Lambolez, B. Cereb. Cortex (2006) [Pubmed]
  42. Localization of cholecystokinin A and cholecystokinin B-gastrin receptors in the human stomach. Reubi, J.C., Waser, B., Läderach, U., Stettler, C., Friess, H., Halter, F., Schmassmann, A. Gastroenterology (1997) [Pubmed]
  43. Cholecystokinin and somatostatin in Alzheimer's disease postmortem cerebral cortex. Mazurek, M.F., Beal, M.F. Neurology (1991) [Pubmed]
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