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Gene Review

Cck  -  cholecystokinin

Rattus norvegicus

Synonyms: CCK, Cholecystokinin
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Disease relevance of Cck

  • The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis [1].
  • Rin5F cells, derived from a rat insulinoma, and STC-1 cells, derived from a murine intestinal tumor, process pro-CCK mainly to amidated CCK 8 [2].
  • We conclude that CCK exerts protective activity against ethanol-induced damage and that this effect is mediated through specific CCKA receptors and hyperemia involving NO [3].
  • Pretreating neostriatal neurons with 500 ng/ml pertussis toxin did not prevent CCK-8 from evoking cationic currents [4].
  • Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced colitis in rats: role of capsaicin-sensitive vagal afferent fibers [5].

Psychiatry related information on Cck


High impact information on Cck

  • These results indicate that gastric leptin may be involved in early CCK-mediated effects activated by food intake, possibly including satiety [11].
  • Characterization and inhibition of a cholecystokinin-inactivating serine peptidase [12].
  • We demonstrate here that the administration of an antiemetic to rats significantly attenuates the food intake reduction caused by exogenously administered CCK but does not increase normal consumption [13].
  • Moreover, the disappearance of gastrin from the pancreas during the first weeks after birth parallels the appearance of CCK in the intestine [14].
  • Although phosphorylation has received most attention, tyrosine-O-sulphation is also common and has been closely investigated in the hormones gastrin and cholecystokinin (CCK) [14].

Chemical compound and disease context of Cck


Biological context of Cck

  • The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites [19].
  • We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells [1].
  • Several affected cell lines displayed about 80% reduction in CCK content in early passages after transfection [2].
  • Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes [20].
  • Under current-clamp recordings, CCK-8 depolarized DA neurons and triggered action potentials [21].

Anatomical context of Cck


Associations of Cck with chemical compounds

  • The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety [26].
  • In the present study, we investigated gastrin (CCK-B) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6, comparing it to normal rat pancreas, and we also characterized CCK receptor subtypes in this tumor [19].
  • Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons [27].
  • The effect of devazepide was prevented by cholecystokinin octapeptide (CCK-8; 40 micrograms kg-1, s.c) as well as by the selective glucocorticosteroid GII receptor agonist, dexamethasone (30 micrograms kg-1, s.c.) 4 [28].
  • Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurones in the dorsal raphe of the rat brain [29].

Physical interactions of Cck


Enzymatic interactions of Cck


Co-localisations of Cck


Regulatory relationships of Cck


Other interactions of Cck

  • Prohormone convertase 1 is necessary for the formation of cholecystokinin 8 in Rin5F and STC-1 cells [2].
  • In a previous study, we developed a new antagonist radioligand, 125I-Bolton-Hunter-labeled JMV-179, for the CCK-A receptor (CCK-AR), to analyze CCK antagonist binding sites in pancreatic plasma membranes [22].
  • SS mRNA and peptide levels significantly decreased in the PC/RSC and hippocampus but not in the frontal cortex 3 days after 0.5 mg/kg MK-801 treatment whereas CCK mRNA and peptide levels significantly decreased in all of the brain regions examined [39].
  • Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY [40].
  • PC2 knockout mouse brains had less CCK 8 than wild-type, although a substantial amount of CCK was still present [41].

Analytical, diagnostic and therapeutic context of Cck


  1. Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. Roles in cell injury processes of pancreatitis. Gukovskaya, A.S., Gukovsky, I., Jung, Y., Mouria, M., Pandol, S.J. J. Biol. Chem. (2002) [Pubmed]
  2. Prohormone convertase 1 is necessary for the formation of cholecystokinin 8 in Rin5F and STC-1 cells. Yoon, J., Beinfeld, M.C. J. Biol. Chem. (1997) [Pubmed]
  3. Exogenous and endogenous cholecystokinin protects gastric mucosa against the damage caused by ethanol in rats. Konturek, S.J., Brzozowski, T., Pytko-Polonczyk, J., Drozdowicz, D. Eur. J. Pharmacol. (1995) [Pubmed]
  4. The excitatory effect of cholecystokinin on rat neostriatal neurons: ionic and molecular mechanisms. Wu, T., Wang, H.L. Eur. J. Pharmacol. (1996) [Pubmed]
  5. Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced colitis in rats: role of capsaicin-sensitive vagal afferent fibers. Bozkurt, A., Cakir, B., Ercan, F., Yeğen, B.C. Regul. Pept. (2003) [Pubmed]
  6. Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin. McMinn, J.E., Sindelar, D.K., Havel, P.J., Schwartz, M.W. Endocrinology (2000) [Pubmed]
  7. Differential role of cholecystokinin receptor subtypes in opioid modulation of ongoing maternal behavior. Miranda-Paiva, C.M., Felicio, L.F. Pharmacol. Biochem. Behav. (1999) [Pubmed]
  8. Regulation of cholecystokinin receptors in the hypothalamus of the rat: reciprocal changes in magnocellular nuclei induced by food deprivation and dehydration. O'Shea, R.D., Gundlach, A.L. J. Neuroendocrinol. (1993) [Pubmed]
  9. Cholecystokinin and leptin act synergistically to reduce body weight. Matson, C.A., Reid, D.F., Cannon, T.A., Ritter, R.C. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2000) [Pubmed]
  10. Decrease in exploratory behavior in naturally occurring cholecystokinin (CCK)-A receptor gene knockout rats. Kobayashi, S., Ohta, M., Miyasaka, K., Funakoshi, A. Neurosci. Lett. (1996) [Pubmed]
  11. The stomach is a source of leptin. Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J.P., Bortoluzzi, M.N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., Lewin, M.J. Nature (1998) [Pubmed]
  12. Characterization and inhibition of a cholecystokinin-inactivating serine peptidase. Rose, C., Vargas, F., Facchinetti, P., Bourgeat, P., Bambal, R.B., Bishop, P.B., Chan, S.M., Moore, A.N., Ganellin, C.R., Schwartz, J.C. Nature (1996) [Pubmed]
  13. An antiemetic is antidotal to the satiety effects of cholecystokinin. Moore, B.O., Deutsch, J.A. Nature (1985) [Pubmed]
  14. Complete tyrosine-O-sulphation of gastrin in neonatal rat pancreas. Brand, S.J., Andersen, B.N., Rehfeld, J.F. Nature (1984) [Pubmed]
  15. Involvement of spinal cholecystokininB receptors in mediating neurotensin hyperalgesia from the medullary nucleus raphe magnus in the rat. Urban, M.O., Smith, D.J., Gebhart, G.F. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  16. Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. Schwarzer, C., Williamson, J.M., Lothman, E.W., Vezzani, A., Sperk, G. Neuroscience (1995) [Pubmed]
  17. Type B cholecystokinin receptors on rat glioma C6 cells. Binding studies and measurement of intracellular calcium mobilization. Kaufmann, R., Lindschau, C., Schöneberg, T., Haller, H., Henklein, P., Boomgaarden, M., Ott, T. Brain Res. (1994) [Pubmed]
  18. Cholecystokinin octapeptide reverses the kappa-opioid-receptor-mediated depression of calcium current in rat dorsal root ganglion neurons. Xu, T., Liu, N.J., Li, C.Q., Shangguan, Y., Yu, Y.X., Kang, H.G., Han, J.S. Brain Res. (1996) [Pubmed]
  19. Novel expression of gastrin (cholecystokinin-B) receptors in azaserine-induced rat pancreatic carcinoma: receptor determination and characterization. Zhou, W., Povoski, S.P., Longnecker, D.S., Bell, R.H. Cancer Res. (1992) [Pubmed]
  20. Differential roles for cholecystokinin a receptors in energy balance in rats and mice. Bi, S., Scott, K.A., Kopin, A.S., Moran, T.H. Endocrinology (2004) [Pubmed]
  21. CCK-8 excites substantia nigra dopaminergic neurons by increasing a cationic conductance. Wu, T., Wang, H.L. Neurosci. Lett. (1994) [Pubmed]
  22. Photoaffinity labeling of rat pancreatic cholecystokinin type A receptor antagonist binding sites demonstrates the presence of a truncated cholecystokinin type A receptor. Poirot, S.S., Escrieut, C., Dufresne, M., Martinez, J., Bouisson, M., Vaysse, N., Fourmy, D. Mol. Pharmacol. (1994) [Pubmed]
  23. Cholecystokinin modulates the release of dopamine from the anterior and posterior nucleus accumbens by two different mechanisms. Marshall, F.H., Barnes, S., Hughes, J., Woodruff, G.N., Hunter, J.C. J. Neurochem. (1991) [Pubmed]
  24. Genetic inactivation of prohormone convertase (PC1) causes a reduction in cholecystokinin (CCK) levels in the hippocampus, amygdala, pons and medulla in mouse brain that correlates with the degree of colocalization of PC1 and CCK mRNA in these structures in rat brain. Cain, B.M., Connolly, K., Blum, A.C., Vishnuvardhan, D., Marchand, J.E., Zhu, X., Steiner, D.F., Beinfeld, M.C. J. Neurochem. (2004) [Pubmed]
  25. Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons. Martínez-Guijarro, F.J., Briñón, J.G., Blasco-Ibáñez, J.M., Okazaki, K., Hidaka, H., Alonso, J.R. Hippocampus. (1998) [Pubmed]
  26. Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Singh, L., Lewis, A.S., Field, M.J., Hughes, J., Woodruff, G.N. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  27. Neurochemical characterization of excitotoxin lesions in the cerebral cortex. Beal, M.F., Swartz, K.J., Finn, S.F., Mazurek, M.F., Kowall, N.W. J. Neurosci. (1991) [Pubmed]
  28. Impairment of stress adaptive behaviours in rats by the CCKA receptor antagonist, devazepide. Hernando, F., Fuentes, J.A., Ruiz-Gayo, M. Br. J. Pharmacol. (1996) [Pubmed]
  29. Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurones in the dorsal raphe of the rat brain. Boden, P.R., Woodruff, G.N., Pinnock, R.D. Br. J. Pharmacol. (1991) [Pubmed]
  30. Structure-activity function for binding and signaling in CHO-K1 and COS-7 cells expressing the cholecystokinin A receptor. Tsunoda, Y., Song, I., Taylor, L.P., Owyang, C. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. Mutation of Asn-391 within the conserved NPXXY motif of the cholecystokinin B receptor abolishes Gq protein activation without affecting its association with the receptor. Galés, C., Kowalski-Chauvel, A., Dufour, M.N., Seva, C., Moroder, L., Pradayrol, L., Vaysse, N., Fourmy, D., Silvente-Poirot, S. J. Biol. Chem. (2000) [Pubmed]
  32. Agonists and antagonists of regulatory peptides as tools to study regulation of pancreatic exocrine secretion, cell proliferation and gene expression. Burghardt, B., Kisfalvi, K., Varga, G., Papp, M. Scand. J. Gastroenterol. Suppl. (1998) [Pubmed]
  33. Visualization of neuropeptide-binding sites on individual telencephalic neurons of the rat. Krisch, B., Buchholz, C., Mentlein, R., Turzynski, A. Cell Tissue Res. (1993) [Pubmed]
  34. Somatostatin 28 interacts with CCK receptor in brain and pancreas. Tahiri-Jouti, N., Dufresne, M., Viguerie, N., Fourmy, D., Estève, J.P., Rivier, J., Moroder, L., Susini, C., Vaysse, N. Neuropeptides (1991) [Pubmed]
  35. Assessment of the role of "enkephalinase" in cholecystokinin inactivation. Zuzel, K.A., Rose, C., Schwartz, J.C. Neuroscience (1985) [Pubmed]
  36. Ultrastructural studies on peptides in the dorsal horn of the spinal cord--I. Co-existence of galanin with other peptides in primary afferents in normal rats. Zhang, X., Nicholas, A.P., Hökfelt, T. Neuroscience (1993) [Pubmed]
  37. Depolarizing action of cholecystokinin on rat supraoptic neurones in vitro. Jarvis, C.R., Bourque, C.W., Renaud, L.P. J. Physiol. (Lond.) (1992) [Pubmed]
  38. Vasoactive intestinal polypeptide stimulates cholecystokinin secretion in perfused rat duodenum. Funakoshi, A., Nakano, I., Miyazaki, K. Tohoku J. Exp. Med. (1989) [Pubmed]
  39. Clozapine but not haloperidol suppresses the changes in the levels of neuropeptides in MK-801-treated rat brain regions. Arif, M., Ahmed, M.M., Kumabe, Y., Hoshino, H., Chikuma, T., Kato, T. Neurochem. Int. (2006) [Pubmed]
  40. Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. Sutin, E.L., Jacobowitz, D.M. J. Comp. Neurol. (1988) [Pubmed]
  41. Distribution and colocalization of cholecystokinin with the prohormone convertase enzymes PC1, PC2, and PC5 in rat brain. Cain, B.M., Connolly, K., Blum, A., Vishnuvardhan, D., Marchand, J.E., Beinfeld, M.C., Vishnuvardham, D. J. Comp. Neurol. (2003) [Pubmed]
  42. Mediation by CCKB receptors of the CCK-evoked hyperaemia in rat gastric mucosa. Heinemann, A., Jocic, M., Holzer-Petsche, U., Pethö, G., Peskar, B.M., Horwell, D.C., Holzer, P. Br. J. Pharmacol. (1995) [Pubmed]
  43. Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor. Pu, S.F., Zhuang, H.X., Han, J.S. Brain Res. (1994) [Pubmed]
  44. A novel role for cholecystokinin: regulation of mesenteric vascular resistance. Sánchez-Fernández, C., González, M.C., Beart, P.M., Mercer, L.D., Ruiz-Gayo, M., Fernández-Alfonso, M.S. Regul. Pept. (2004) [Pubmed]
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