Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Cholecystokinin-1 Receptor

  • Laurence J. MillerEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_273


Historical Background

The hormone cholecystokinin (CCK) was discovered in 1928 by Ivy and Oldberg, based on its ability to stimulate gallbladder contraction. Fifteen years later, Harper and Raper described a factor capable of stimulating pancreatic exocrine secretion (pancreozymin). When Jorpes and Mutt finally isolated the CCK peptide from porcine duodenum in 1966, it became clear that this single hormone was responsible for both of these classical physiological gastrointestinal regulatory activities. Many years later, in 1992, the receptor mediating these effects was finally identified and characterized as a family A guanine nucleotide-binding protein (G protein)-coupled receptor, the CCK-1 receptor (Liddle 1994). Of interest, the cDNA encoding this receptor was initially cloned and described in the...

This is a preview of subscription content, log in to check access.


  1. Cawston EE, Miller LJ. Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor. Br J Pharmacol. 2010;159:1009–21. PMID: 22467877.PubMedCrossRefGoogle Scholar
  2. Cawston EE, Lam PC, Harikumar KG, Dong M, Ball AM, Augustine ML, Akgün E, Portoghese PS, Orry A, Abagyan R, Sexton PM, Miller LJ. Molecular basis for binding and subtype selectivity of 1,4-benzodiazepine antagonist ligands of the cholecystokinin receptor. J Biol Chem. 2012;287:18618–35. PMID: 22467877.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Gao F, Sexton PM, Christopoulos A, Miller LJ. Benzodiazepine ligands can act as allosteric modulators of the Type 1 cholecystokinin receptor. Bioorg Med Chem Lett. 2008;18:4401–4.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Harikumar KG, Cawston EE, Lam PC, Patil A, Orry A, Henke BR, Abagyan R, Christopoulos A, Sexton PM, Miller LJ. Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor. J Biol Chem. 2013;288:21082–95. PMID: 23754289.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Klueppelberg UG, Gates LK, Gorelick FS, Miller LJ. Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor. J Biol Chem. 1991;266:2403–8.PubMedPubMedCentralGoogle Scholar
  6. Korner M, Miller LJ. Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide hormone receptors. Am J Pathol. 2009;175:461–72.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Liddle RA. Cholecystokinin. In: Walsh JH, Dockray GJ, editors. Gut peptides: biochemistry and physiology. New York: Raven; 1994. p. 175–216.Google Scholar
  8. Miller LJ, Gao F. Structural basis of cholecystokinin receptor binding and regulation. Pharmacol Ther. 2008;119:83–95.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Noble F, Wank SA, Crawley JN, Bradwejn J, Seroogy KB, Hamon M, et al. International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev. 1999;51:745–81.PubMedPubMedCentralGoogle Scholar
  10. Reubi JC, Schaer JC, Waser B. Cholecystokinin(CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res. 1997;57:1377–86.PubMedPubMedCentralGoogle Scholar
  11. Roettger BF, Rentsch RU, Pinon DI, Holicky E, Hadac E, Larkin JM, et al. Dual pathways of internalization of the cholecystokinin receptor. J Cell Biol. 1993;128:1029–41.CrossRefGoogle Scholar
  12. Sabbatini ME, Bi Y, Ji B, Ernst SA, Williams JA. CCK activates RhoA and Rac1 differentially through Galpha13 and Galphaq in mouse pancreatic acini. Am J Phys. 2010;298:C592–601. PMID: 19940064.CrossRefGoogle Scholar
  13. Sayegh AI, Washington MC, Raboin SJ, Aglan AH, Reeve Jr JR. CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: not all forms of cholecystokinin have equal bioactivity. Peptides. 2014;55:120–5. PMID: 24607725.PubMedCrossRefGoogle Scholar
  14. Whalen EJ, Rajagopal S, Lefkowitz RJ. Therapeutic potential of beta-arrestin- and G protein-biased agonists. Trends Mol Med. 2011;17:126–39.PubMedCrossRefGoogle Scholar
  15. Williams JA. Intracellular signaling mechanisms activated by cholecystokinin-regulating synthesis and secretion of digestive enzymes in pancreatic acinar cells. Annu Rev Physiol. 2001;63:77–97.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pharmacology and Experimental Therapeutics and Department of Internal Medicine, Division of GastroenterologyMayo ClinicScottsdaleUSA