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Gene Review

CCKBR  -  cholecystokinin B receptor

Homo sapiens

Synonyms: CCK-B, CCK-B receptor, CCK-BR, CCK2-R, CCK2R, ...
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Disease relevance of CCKBR


Psychiatry related information on CCKBR


High impact information on CCKBR

  • The canine and human CCK-B/gastrin receptors share 90% amino-acid identity and have similar agonist affinities [10].
  • The development of potent and selective antagonists for CCK-A (MK-329) and CCK-B (L-365,260) receptors now allows these issues to be addressed [11].
  • These results suggest that endogenous CCK causes satiety by an agonist action on CCK-B receptors in the brain [11].
  • The CCK-A antagonist MK-329 and the CCK-B antagonist L-365,260 increased food intake in partially satiated rats and postponed the onset of satiety; however, L-365,260 was 100 times more potent than MK-329 in increasing feeding and preventing satiety [11].
  • Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors [12].

Chemical compound and disease context of CCKBR


Biological context of CCKBR


Anatomical context of CCKBR


Associations of CCKBR with chemical compounds

  • Both CCK-8 and gastrin I markedly augmented phosphoinositide hydrolysis and cytosolic free calcium levels in the CHO transfectants, indicating that the cloned CCK-B receptor could functionally couple with intracellular signaling molecules [26].
  • Substitution of Phe347 in TM-VI with alanine produced a mutant receptor that displays the same affinity and selectivity as the wild-type receptor for agonists, but a slightly increased affinity for the selective CCKB antagonist L-365,260 [27].
  • Ser82 was further changed into Asp, Thr, or Ala to determine the specificity of this position in Gs coupling by the CCK-BR [28].
  • Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: synergism with pharmacological levels of melatonin [13].
  • Intravenous injection of the cholecystokinin (CCK)-B receptor agonist, pentagastrin, produces robust, dose-dependent release of adrenocorticotropin (ACTH) and cortisol, supporting the hypothesis that CCK-B agonists pharmacologically activate the hypothalamic-pituitary-adrenal (HPA) axis [29].

Physical interactions of CCKBR

  • Using the NOE-generated intermolecular contact points, extensive MD simulations of CCK-8 bound to the CCK2 receptor were carried out [30].
  • Our study has identified the presence of CCKB/gastrin receptor isoforms in different cellular locations and may help toward understanding the complex autocrine and intracrine pathways mediated by gastrin peptides [31].
  • Using surface plasmon resonance analysis, we identified a highly conserved ITIM motif, containing the tyrosine residue 438, located in the C-terminal intracellular tail of the CCK2R which directly interacts with the SHP-2 SH2 domains [32].
  • Taken together, these results suggest that the CCK2 receptor is coupled to two G proteins and that Phe347 and the cluster of basic residues K333/K334/R335 probably play a key role in Gq protein stimulation leading to inositol phosphate production but not in activation of the G protein coupled to phospholipase A2 [33].

Co-localisations of CCKBR


Regulatory relationships of CCKBR


Other interactions of CCKBR


Analytical, diagnostic and therapeutic context of CCKBR


  1. What are the pancreatic target cells for gastrin and its CCKB receptor? Is this a couple for cancerous cells? Morisset, J., Lainé, J., Biernat, M., Julien, S. Med. Sci. Monit. (2004) [Pubmed]
  2. Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin. Iwase, K., Evers, B.M., Hellmich, M.R., Guo, Y.S., Higashide, S., Kim, H.J., Townsend, C.M. Gastroenterology (1997) [Pubmed]
  3. Cholecystokinin(CCK)-A and CCK-B/gastrin receptors in human tumors. Reubi, J.C., Schaer, J.C., Waser, B. Cancer Res. (1997) [Pubmed]
  4. 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]
  5. Association studies of the CT repeat polymorphism in the 5' upstream region of the cholecystokinin B receptor gene with panic disorder and schizophrenia in Japanese subjects. Hattori, E., Yamada, K., Toyota, T., Yoshitsugu, K., Toru, M., Shibuya, H., Yoshikawa, T. Am. J. Med. Genet. (2001) [Pubmed]
  6. Cholecystokinin-induced anxiety: how is it reflected in studies on exploratory behaviour? Harro, J., Vasar, E. Neuroscience and biobehavioral reviews. (1991) [Pubmed]
  7. Pentagastrin has panic-inducing properties in obsessive compulsive disorder. de Leeuw, A.S., Den Boer, J.A., Slaap, B.R., Westenberg, H.G. Psychopharmacology (Berl.) (1996) [Pubmed]
  8. Cholecystokinin-B (CCK-B) receptor antagonists improve "aged" sleep: a new class of sleep modulators? Crespi, F. Methods and findings in experimental and clinical pharmacology. (1999) [Pubmed]
  9. Effects of the cholecystokinin agonist pentagastrin in patients with generalized anxiety disorder. Brawman-Mintzer, O., Lydiard, R.B., Bradwejn, J., Villarreal, G., Knapp, R., Emmanuel, N., Ware, M.R., He, Q., Ballenger, J.C. The American journal of psychiatry. (1997) [Pubmed]
  10. A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists. Beinborn, M., Lee, Y.M., McBride, E.W., Quinn, S.M., Kopin, A.S. Nature (1993) [Pubmed]
  11. Postponement of satiety by blockade of brain cholecystokinin (CCK-B) receptors. Dourish, C.T., Rycroft, W., Iversen, S.D. Science (1989) [Pubmed]
  12. Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma. Weinberg, D.S., Ruggeri, B., Barber, M.T., Biswas, S., Miknyocki, S., Waldman, S.A. J. Clin. Invest. (1997) [Pubmed]
  13. 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]
  14. Pentagastrin infusions in patients with panic disorder. I. Symptoms and cardiovascular responses. Abelson, J.L., Nesse, R.M. Biol. Psychiatry (1994) [Pubmed]
  15. The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients. van Megen, H.J., Westenberg, H.G., den Boer, J.A., Slaap, B., van Es-Radhakishun, F., Pande, A.C. Psychopharmacology (Berl.) (1997) [Pubmed]
  16. Meningiomas expressing and responding to cholecystokinin (CCK). Oikonomou, E., Machado, A.L., Buchfelder, M., Adams, E.F. J. Neurooncol. (2005) [Pubmed]
  17. Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. Yamada, K., Hattori, E., Shimizu, M., Sugaya, A., Shibuya, H., Yoshikawa, T. Journal of neural transmission (Vienna, Austria : 1996) (2001) [Pubmed]
  18. A segment of five amino acids in the second extracellular loop of the cholecystokinin-B receptor is essential for selectivity of the peptide agonist gastrin. Silvente-Poirot, S., Wank, S.A. J. Biol. Chem. (1996) [Pubmed]
  19. Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization. de Weerth, A., Jonas, L., Schade, R., Schöneberg, T., Wolf, G., Pace, A., Kirchhoff, F., Schulz, M., Heinig, T., Greten, H., von Schrenck, T. Eur. J. Clin. Invest. (1998) [Pubmed]
  20. Linkage assignment of eleven genes to the porcine genome. Hu, Z., Rohrer, G.A., Stone, R.T., Rutherford, M., Osinski, M.A., Pampusch, M.S., Murtaugh, M.P., Brown, D.R., Beattie, C.W. Mamm. Genome (1997) [Pubmed]
  21. CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology. Noble, F., Roques, B.P. Prog. Neurobiol. (1999) [Pubmed]
  22. In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging. Aloj, L., Caracò, C., Panico, M., Zannetti, A., Del Vecchio, S., Tesauro, D., De Luca, S., Arra, C., Pedone, C., Morelli, G., Salvatore, M. J. Nucl. Med. (2004) [Pubmed]
  23. 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]
  24. Cholecystokinin receptors in human pancreas and gallbladder muscle: a comparative study. Tang, C., Biemond, I., Lamers, C.B. Gastroenterology (1996) [Pubmed]
  25. Gastrin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer cells. Sethi, T., Rozengurt, E. Cancer Res. (1992) [Pubmed]
  26. Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin. Ito, M., Matsui, T., Taniguchi, T., Tsukamoto, T., Murayama, T., Arima, N., Nakata, H., Chiba, T., Chihara, K. J. Biol. Chem. (1993) [Pubmed]
  27. Binding sites and transduction process of the cholecystokininB receptor: involvement of highly conserved aromatic residues of the transmembrane domains evidenced by site-directed mutagenesis. Jagerschmidt, A., Guillaume, N., Roques, B.P., Noble, F. Mol. Pharmacol. (1998) [Pubmed]
  28. Single amino acid substitution of serine82 to asparagine in first intracellular loop of human cholecystokinin (CCK)-B receptor confers full cyclic AMP responses to CCK and gastrin. Wu, S.V., Yang, M., Avedian, D., Birnbaumer, M., Walsh, J.H. Mol. Pharmacol. (1999) [Pubmed]
  29. Hypothalamic-pituitary adrenal response to cholecystokinin-B receptor agonism is resistant to cortisol feedback inhibition. Abelson, J.L., Young, E.A. Psychoneuroendocrinology (2003) [Pubmed]
  30. Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor. Giragossian, C., Mierke, D.F. Biochemistry (2002) [Pubmed]
  31. Expression of CCKB/gastrin receptor isoforms in gastro-intestinal tumour cells. Watson, S.A., Clarke, P.A., Smith, A.M., Varro, A., Michaeli, D., Grimes, S., Caplin, M., Hardcastle, J.D. Int. J. Cancer (1998) [Pubmed]
  32. An ITIM-like motif within the CCK2 receptor sequence required for interaction with SHP-2 and the activation of the AKT pathway. Vatinel, S., Ferrand, A., Lopez, F., Kowalski-Chauvel, A., Est??ve, J.P., Fourmy, D., Dufresne, M., Seva, C. Biochim. Biophys. Acta (2006) [Pubmed]
  33. Further evidence that the CCK2 receptor is coupled to two transduction pathways using site-directed mutagenesis. Pommier, B., Marie-Claire, C., Da Nascimento, S., Wang, H.L., Roques, B.P., Noble, F. J. Neurochem. (2003) [Pubmed]
  34. Presence and localization of CCK receptor subtypes in calf pancreas. Morisset, J., Lainé, J., Bourassa, J., Lessard, M., Rome, V., Guilloteau, P. Regul. Pept. (2003) [Pubmed]
  35. Cholecystokinin increases intracellular Ca2+ concentration in the Human JURKAT T Lymphocyte cell line. Lignon, M.F., Bernad, N., Martinez, J. Eur. J. Pharmacol. (1993) [Pubmed]
  36. Cellular localization of cholecystokinin receptors as the molecular basis of the periperal regulation of acid secretion. Schmidt, W.E., Schmitz, F. Pharmacol. Toxicol. (2002) [Pubmed]
  37. Essential interaction of Egr-1 at an islet-specific response element for basal and gastrin-dependent glucagon gene transactivation in pancreatic alpha-cells. Leung-Theung-Long, S., Roulet, E., Clerc, P., Escrieut, C., Marchal-Victorion, S., Ritz-Laser, B., Philippe, J., Pradayrol, L., Seva, C., Fourmy, D., Dufresne, M. J. Biol. Chem. (2005) [Pubmed]
  38. SRC regulates constitutive internalization and rapid resensitization of a cholecystokinin 2 receptor splice variant. Chao, C., Ives, K.L., Goluszko, E., Kolokoltsov, A.A., Davey, R.A., Townsend, C.M., Hellmich, M.R. J. Biol. Chem. (2005) [Pubmed]
  39. First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells. Wu, V., Yang, M., McRoberts, J.A., Ren, J., Seensalu, R., Zeng, N., Dagrag, M., Birnbaumer, M., Walsh, J.H. J. Biol. Chem. (1997) [Pubmed]
  40. Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies. Behr, T.M., Béhé, M.P. Seminars in nuclear medicine. (2002) [Pubmed]
  41. The human gastrin/cholecystokinin receptors: type B and type C expression in colonic tumors and cell lines. Biagini, P., Monges, G., Vuaroqueaux, V., Parriaux, D., Cantaloube, J.F., De Micco, P. Life Sci. (1997) [Pubmed]
  42. 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]
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