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Gene Review

Calcr  -  calcitonin receptor

Rattus norvegicus

Synonyms: C1A/C1B, CT-R, Calcitonin receptor
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Disease relevance of Calcr


High impact information on Calcr

  • Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells [2].
  • Furthermore, it was found that alpha C1A-C1B bound to a peptide containing the C2 domain of PKC alpha [3].
  • The alpha C1A-C1B domain also activated conventional PKC beta I, -beta II, and -gamma isoforms, but not novel PKC delta or -epsilon [3].
  • CONCLUSION: Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR [4].
  • TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone [4].

Chemical compound and disease context of Calcr

  • Following a 20-day period, locally released PGE2 at doses of 0.1 and 0.05 mg/day appears to affect alveolar bone resorption in the periodontium of rats, as the number of multinucleated cells expressing TRAP and CTR are significantly reduced [5].

Biological context of Calcr


Anatomical context of Calcr

  • CONCLUSIONS: CTR C1a protein expression has been identified in the ureteric ducts in the metanephros and both isoforms expressed in the distal portions of the developing nephrons and collecting ducts [6].
  • RESULTS: The CTR C1a isoform is expressed in the ureteric ducts of the metanephros and both isoforms are expressed in the developing distal convoluted tubules, ascending limbs of the loop of Henle and collecting ducts in the postnatal rat kidney [6].
  • Ontogeny of calcitonin receptor mRNA and protein in the developing central nervous system of the rat [11].
  • However, we detected CTR immunoreactivity in several additional brain areas, as the ventromedial, lateral and posterior hypothalamus, where CT binding has not yet been described [12].
  • Then, porcine RAMPs, CRLR and CTR were expressed in COS-7 or porcine vascular smooth muscle cells, and the resulting receptor complexes were analyzed by the cyclic adenosine 3,5-monophosphate (cAMP) production assay [13].

Associations of Calcr with chemical compounds

  • Based on these findings, it is proposed that the activating conformational change in PKC alpha results from the dissociation of intra-molecular interactions between the alpha C1A-C1B domain and the C2 domain [3].
  • The minimal chain length required to activate adenylate cyclase in rat renal plasma membranes was between 12-18 amino acids, and the minimal chain length required to affect the CT receptor binding was between 6-12 amino acids, near the C-terminus [14].
  • In cocultures of clonal marrow stromal cells (MS1) and normal mouse spleen cells, both 1,25-dihydroxyvitamin D3 and rat PTH (rPTH)-(1-34) can induce the formation of tartrate-resistant acid phosphatase- and calcitonin receptor-positive multinucleated osteoclast-like cells, which can attach to dentine slices and produce resorption pits [15].
  • Pretreatment of hyperglycemic rats with the CT synthesis inhibitor metyrapone or the CT receptor antagonist, RU38486, prevents hyperglycemic aggravation of ischemic neuronal damage [16].
  • Autoradiography of polyacrylamide gels of cross-linked calcitonin receptor showed only three protein bands specifically binding salmon calcitonin [17].

Physical interactions of Calcr


Regulatory relationships of Calcr

  • Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat [19].
  • Heterologous desensitization was also seen, as manifested by decreased calcitonin (CT)-stimulated adenylate cyclase activity with normal CT receptor binding [20].

Other interactions of Calcr

  • In this study, the expression of receptors for calcitonin (CTR), the CTR C1a and C1b isoforms, was investigated during development of the fetal rat central nervous system (CNS) by using in situ hybridization and immunohistochemistry [11].
  • Using an in vitro assay containing only purified recombinant proteins and the phorbol ester, 4 beta-12-O-tetradecanoylphorbol-13-acetate (TPA), but lacking lipids, it was found that PKC alpha bound specifically, and with high affinity, to a alpha C1A-C1B fusion protein of the same isozyme [3].
  • Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells [21].
  • The double detection of these two antigen molecules with osteoclast-specific antigen and with calcitonin receptor, using a fluorescence-activated cell sorter or autoradiography technique, revealed that LFA-1 and ICAM-1 were expressed on the preosteoclasts [22].

Analytical, diagnostic and therapeutic context of Calcr


  1. Effects of transforming growth factor beta 1 on the regulation of osteoclastic development and function. Hattersley, G., Chambers, T.J. J. Bone Miner. Res. (1991) [Pubmed]
  2. Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells. Chausmer, A.B., Stevens, M.D., Severn, C. Science (1982) [Pubmed]
  3. Regulation of PKC alpha activity by C1-C2 domain interactions. Slater, S.J., Seiz, J.L., Cook, A.C., Buzas, C.J., Malinowski, S.A., Kershner, J.L., Stagliano, B.A., Stubbs, C.D. J. Biol. Chem. (2002) [Pubmed]
  4. Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis. Romas, E., Bakharevski, O., Hards, D.K., Kartsogiannis, V., Quinn, J.M., Ryan, P.F., Martin, T.J., Gillespie, M.T. Arthritis Rheum. (2000) [Pubmed]
  5. Local application of prostaglandin E2 reduces trap, calcitonin receptor and metalloproteinase-2 immunoreactivity in the rat periodontium. Ramirez-Yañez, G.O., Seymour, G.J., Symons, A.L. Arch. Oral Biol. (2005) [Pubmed]
  6. Calcitonin receptor isoforms expressed in the developing rat kidney. Tikellis, C., Xuereb, L., Casley, D., Brasier, G., Cooper, M.E., Wookey, P.J. Kidney Int. (2003) [Pubmed]
  7. The in vivo effect of adrenomedullin on rat dural and pial arteries. Juhl, L., Petersen, K.A., Larsen, E.H., Jansen-Olesen, I., Olesen, J. Eur. J. Pharmacol. (2006) [Pubmed]
  8. Calcitonin expression in rat anterior pituitary gland is regulated by ovarian steroid hormones. Sun, Y.P., Lee, T.J., Shah, G.V. Endocrinology (2002) [Pubmed]
  9. Loss of calcitonin binding in rat is not related to calcitonin receptor gene abnormality. Nakamura, M., Yang, Q., Gouda, T., Takehara, A., Ohta, H., Miyajima, M., Kakudo, K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  10. Chemo-enzymatic synthesis and structure-activity study of artificially N-glycosylated eel calcitonin derivatives with a complex type oligosaccharide. Haneda, K., Tagashira, M., Yoshino, E., Takeuchi, M., Inazu, T., Toma, K., Iijima, H., Isogai, Y., Hori, M., Takamatsu, S., Fujibayashi, Y., Kobayashi, K., Takeuchi, M., Yamamoto, K. Glycoconj. J. (2004) [Pubmed]
  11. Ontogeny of calcitonin receptor mRNA and protein in the developing central nervous system of the rat. Tolcos, M., Tikellis, C., Rees, S., Cooper, M., Wookey, P. J. Comp. Neurol. (2003) [Pubmed]
  12. Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Becskei, C., Riediger, T., Zünd, D., Wookey, P., Lutz, T.A. Brain Res. (2004) [Pubmed]
  13. Specificity of porcine calcitonin receptor and calcitonin receptor-like receptor in the presence of receptor-activity-modifying proteins. Kikumoto, K., Katafuchi, T., Minamino, N. Hypertens. Res. (2003) [Pubmed]
  14. Adenylate cyclase activation and competitive binding with renal tissue using synthetic eel calcitonin analog and its fragments. Yamamoto, I., Morita, R., Fukunaga, M., Dokoh, S., Shigeno, C., Torizuka, K., Noda, T. Endocrinology (1981) [Pubmed]
  15. Estrogen inhibition of PTH-stimulated osteoclast formation and attachment in vitro: involvement of both PKA and PKC. Liu, B.Y., Wu, P.W., Bringhurst, F.R., Wang, J.T. Endocrinology (2002) [Pubmed]
  16. The glucose paradox of cerebral ischemia: evidence for corticosterone involvement. Payne, R.S., Tseng, M.T., Schurr, A. Brain Res. (2003) [Pubmed]
  17. Purification and characterization of calcitonin receptors in rat kidney membranes by covalent cross-linking techniques. Bouizar, Z., Fouchereau-Peron, M., Taboulet, J., Moukhtar, M.S., Milhaud, G. Eur. J. Biochem. (1986) [Pubmed]
  18. Localization and characterization of renal calcitonin receptors by in vitro autoradiography. Sexton, P.M., Adam, W.R., Moseley, J.M., Martin, T.J., Mendelsohn, F.A. Kidney Int. (1987) [Pubmed]
  19. Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat. Barth, S.W., Riediger, T., Lutz, T.A., Rechkemmer, G. Brain Res. (2004) [Pubmed]
  20. Parathyroid hormone desensitization in renal membranes of vitamin D-deficient rats is associated with a postreceptor defect. Mitchell, J., Tenenhouse, A., Warner, M., Goltzman, D. Endocrinology (1988) [Pubmed]
  21. A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2. Ogata, Y., Kukita, A., Kukita, T., Komine, M., Miyahara, A., Miyazaki, S., Kohashi, O. J. Immunol. (1999) [Pubmed]
  22. Involvement of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in osteoclastogenesis: a possible role in direct interaction between osteoclast precursors. Harada, H., Kukita, T., Kukita, A., Iwamoto, Y., Iijima, T. Endocrinology (1998) [Pubmed]
  23. 3,5 cyclic adenosine monophosphate mediates the salmon calcitonin-induced increase in hypothalamic tyrosine hydroxylase activity. Arbogast, L.A., Shah, G.V., Voogt, J.L. Endocrinology (1999) [Pubmed]
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