Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Calcitonin Receptor

  • Sang-Min Lee
  • Augen A. PioszakEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101586


Historical Background

A hypocalcemic factor that lowers blood calcium in response to hypercalcemia in dogs was first discovered and named by Copp et al. as calcitonin (CT) (Copp et al. 1962). The parafollicular cells of the thyroid in mammals were indicated as the source of calcitonin production (Fig. 1). Calcitonin extracted from thyroid in mammals inhibited the release of calcium from bones (Pondel 2000), and subsequently the amino acid sequence of calcitonin from multiple species was revealed. Salmon calcitonin (sCT) showed the highest potency among the various calcitonins, which resulted in the prevalent use of sCT to understand calcitonin physiology. In 1986, 125I-labeled-sCT binding to isolated rat osteoclasts was visualized by Nicholson et al. indicating that the CT receptor (CTR) was a cell surface receptor highly expressed in osteoclasts (Sexton et al. 1999). In addition, large numbers of 125I-sCT binding sites were...
This is a preview of subscription content, log in to check access.


  1. Bandeira L, Lewiecki EM, Bilezikian JP. Pharmacodynamics and pharmacokinetics of oral salmon calcitonin in the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2016;12(6):681–9.PubMedCrossRefGoogle Scholar
  2. Booe JM, Walker CS, Barwell J, Kuteyi G, Simms J, Jamaluddin MA, et al. Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor. Mol Cell. 2015;58(6):1040–52.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999;56(1):235–42.PubMedCrossRefGoogle Scholar
  4. Copp DH, Cameron EC, Cheney BA, Davidson AG, Henze KG. Evidence for calcitonin – a new hormone from the parathyroid that lowers blood calcium. Endocrinology. 1962;70:638–49.PubMedCrossRefGoogle Scholar
  5. Davey RA, Findlay DM. Calcitonin: physiology or fantasy? J Bone Miner Res Off J Am Soc Bone Miner Res. 2013;28(5):973–9.CrossRefGoogle Scholar
  6. Dong M, Koole C, Wootten D, Sexton PM, Miller LJ. Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs. Br J Pharmacol. 2014;171(5):1085–101.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Findlay DM, Sexton PM, Martin TJ. Calcitonin. Endocrinology: adult and pediatric I. 7th ed: Elsevier; Philadelphia, PA. 2015. p. 1004–17.Google Scholar
  8. Gorn AH, Lin HY, Yamin M, Auron PE, Flannery MR, Tapp DR, et al. Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line. J Clin Invest. 1992;90(5):1726–35.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. 2015;67(3):564–600.PubMedCrossRefGoogle Scholar
  10. Henriksen K, Byrjalsen I, Andersen JR, Bihlet AR, Russo LA, Alexandersen P, et al. A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Bone. 2016;91:122–9.PubMedCrossRefGoogle Scholar
  11. Johansson E, Hansen JL, Hansen AM, Shaw AC, Becker P, Schaffer L, et al. Type II turn of receptor-bound salmon calcitonin revealed by X-ray crystallography. J Biol Chem. 2016;291(26):13689–98.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Keller J, Catala-Lehnen P, Huebner AK, Jeschke A, Heckt T, Lueth A, et al. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun. 2014;5:5215.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Lin HY, Harris TL, Flannery MS, Aruffo A, Kaji EH, Gorn A, et al. Expression cloning of an adenylate cyclase-coupled calcitonin receptor. Science. 1991;254(5034):1022–4.PubMedCrossRefGoogle Scholar
  14. Pondel M. Calcitonin and calcitonin receptors: bone and beyond. Int J Exp Pathol. 2000;81(6):405–22.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Purdue BW, Tilakaratne N, Sexton PM. Molecular pharmacology of the calcitonin receptor. Recept Channels. 2002;8(3–4):243–55.PubMedCrossRefGoogle Scholar
  16. Sexton PM. Central nervous system binding sites for calcitonin and calcitonin gene-related peptide. Mol Neurobiol. 1991;5(2–4):251–73.PubMedCrossRefGoogle Scholar
  17. Sexton PM, Findlay DM, Martin TJ. Calcitonin. Curr Med Chem. 1999;6(11):1067–93.PubMedPubMedCentralGoogle Scholar
  18. Wells G, Chernoff J, Gilligan JP, Krause DS. Does salmon calcitonin cause cancer? A review and meta-analysis. Osteoporos Int. 2016;27(1):13–9.PubMedCrossRefGoogle Scholar
  19. Zaidi M, Datta HK, Moonga BS, MacIntyre I. Evidence that the action of calcitonin on rat osteoclasts is mediated by two G proteins acting via separate post-receptor pathways. J Endocrinol. 1990;126(3):473–81.PubMedCrossRefGoogle Scholar
  20. Zhang Z, Neff L, Bothwell AL, Baron R, Horne WC. Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal adhesion kinase in osteoclasts. Bone. 2002;31(3):359–65.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA