Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Mar 15;250(3):877–882. doi: 10.1042/bj2500877

Human placental calcitonin receptors.

G C Nicholson 1, C S D'Santos 1, T Evans 1, J M Moseley 1, B E Kemp 1, V P Michelangeli 1, T J Martin 1
PMCID: PMC1148937  PMID: 2839149

Abstract

Receptors for the hypocalcaemic hormone, calcitonin (CT), have been identified in a membrane fraction prepared from term human placentae. Binding of 125I-labelled salmon CT (125I-sCT) to the membranes was time- and temperature-dependent, saturable (Bmax. 58 +/- 11 fmol/mg of protein), of high affinity (Kd 80 +/- 21 pM) and poorly reversible. Species-specific CTs and CT analogues competed for 125I-sCT binding with potencies proportional to their known biological potencies. Various unrelated peptide hormones did not compete, indicating that receptor binding was specific for CT. Photoaffinity labelling using a derivatized biologically active sCT analogue, [Arg11,18,3-nitrophenylazide-Lys14]sCT, identified a receptor component of Mr approximately 85,000, comparable with findings in osteoclasts and other target cells. The presence of CT receptors in the human placenta supports other evidence that CT may have a role in the regulation of placental function.

Full text

PDF
882

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arlot-Bonnemains Y., Fouchereau-Peron M., Moukhtar M. S., Milhaud G. Characterization of target organs for calcitonin in lower and higher vertebrates. Comp Biochem Physiol A Comp Physiol. 1983;76(2):377–380. doi: 10.1016/0300-9629(83)90340-7. [DOI] [PubMed] [Google Scholar]
  2. COPP D. H., CHENEY B. Calcitonin-a hormone from the parathyroid which lowers the calcium-level of the blood. Nature. 1962 Jan 27;193:381–382. doi: 10.1038/193381a0. [DOI] [PubMed] [Google Scholar]
  3. Chambers T. J., Magnus C. J. Calcitonin alters behaviour of isolated osteoclasts. J Pathol. 1982 Jan;136(1):27–39. doi: 10.1002/path.1711360104. [DOI] [PubMed] [Google Scholar]
  4. Chausmer A., Stuart C., Stevens M. Identification of testicular cell plasma membrane receptors for calcitonin. J Lab Clin Med. 1980 Nov;96(5):933–938. [PubMed] [Google Scholar]
  5. Copp D. H. Endocrine regulation of calcium metabolism. Annu Rev Physiol. 1970;32:61–86. doi: 10.1146/annurev.ph.32.030170.000425. [DOI] [PubMed] [Google Scholar]
  6. Croley T. E. The intracellular localization of calcium within the mature human placental barrier. Am J Obstet Gynecol. 1973 Dec 1;117(7):926–932. doi: 10.1016/0002-9378(73)90063-x. [DOI] [PubMed] [Google Scholar]
  7. Currie A. J., Fraser H. M., Sharpe R. M. Human placental receptors for luteinizing hormone releasing hormone. Biochem Biophys Res Commun. 1981 Mar 16;99(1):332–338. doi: 10.1016/0006-291x(81)91749-6. [DOI] [PubMed] [Google Scholar]
  8. Eilon G., Perkins J., Viola M. V. Characteristics of a calcitonin-responsive cell line derived from a human osteosarcoma. Cancer Res. 1983 Aug;43(8):3763–3769. [PubMed] [Google Scholar]
  9. Evans T., Brown M. L., Fraser E. D., Northup J. K. Purification of the major GTP-binding proteins from human placental membranes. J Biol Chem. 1986 May 25;261(15):7052–7059. [PubMed] [Google Scholar]
  10. Findlay D. M., Michelangeli V. P., Eisman J. A., Frampton R. J., Moseley J. M., MacIntyre I., Whitehead R., Martin T. J. Calcitonin and 1,25-dihydroxyvitamin D3 receptors in human breast cancer cell lines. Cancer Res. 1980 Dec;40(12):4764–4767. [PubMed] [Google Scholar]
  11. Findlay D. M., Michelangeli V. P., Moseley J. M., Martin T. J. Calcitonin binding and degradation by two cultured human breast cancer cell lines (MCF 7 and T 47D). Biochem J. 1981 May 15;196(2):513–520. doi: 10.1042/bj1960513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Findlay D. M., Michelangeli V. P., Orlowski R. C., Martin T. J. Biological activities and receptor interactions of des-Leu16 salmon and des-Phe16 human calcitonin. Endocrinology. 1983 Apr;112(4):1288–1291. doi: 10.1210/endo-112-4-1288. [DOI] [PubMed] [Google Scholar]
  13. Findlay D. M., deLuise M., Michelangeli V. P., Ellison M., Martin T. J. Properties of a calcitonin receptor and adenylate cyclase in BEN cells, a human cancer cell line. Cancer Res. 1980 Apr;40(4):1311–1317. [PubMed] [Google Scholar]
  14. Fischer J. A., Tobler P. H., Kaufmann M., Born W., Henke H., Cooper P. E., Sagar S. M., Martin J. B. Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7801–7805. doi: 10.1073/pnas.78.12.7801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Forrest S. M., Ng K. W., Findlay D. M., Michelangeli V. P., Livesey S. A., Partridge N. C., Zajac J. D., Martin T. J. Characterization of an osteoblast-like clonal cell line which responds to both parathyroid hormone and calcitonin. Calcif Tissue Int. 1985 Jan;37(1):51–56. doi: 10.1007/BF02557679. [DOI] [PubMed] [Google Scholar]
  16. Fouchereau-Peron M., Moukhtar M. S., Benson A. A., Milhaud G. Characterization of specific receptors for calcitonin in porcine lung. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3973–3975. doi: 10.1073/pnas.78.6.3973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Garel J. M., Care A. D., Barlet J. P. A radioimmunoassay for ovine calcitonin: an evaluation of calcitonin secretion during gestation, lactation and foetal life. J Endocrinol. 1974 Sep;62(3):497–509. doi: 10.1677/joe.0.0620497. [DOI] [PubMed] [Google Scholar]
  18. Goltzman D., Mitchell J. Interaction of calcitonin and calcitonin gene-related peptide at receptor sites in target tissues. Science. 1985 Mar 15;227(4692):1343–1345. doi: 10.1126/science.2983422. [DOI] [PubMed] [Google Scholar]
  19. Hunt N. H., Ellison M., Underwood J. C., Martin T. J. Calcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line. Br J Cancer. 1977 Jun;35(6):777–784. doi: 10.1038/bjc.1977.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hunt N. H., Martin T. J., Michelangeli V. P., Eisman J. A. Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney. J Endocrinol. 1976 Jun;69(3):401–412. [PubMed] [Google Scholar]
  21. Koida M., Nakamuta H., Furukawa S., Orlowski R. C. Abundance and location of 125-I-salmon calcitonin binding site in rat brain. Jpn J Pharmacol. 1980 Aug;30(4):575–577. doi: 10.1254/jjp.30.575. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Littledike E. T., Arnaud C. D., Whipp S. C. Calcitonin secretion in ovine, porcine, and bovine fetuses. Proc Soc Exp Biol Med. 1972 Feb;139(2):428–433. doi: 10.3181/00379727-139-36159. [DOI] [PubMed] [Google Scholar]
  25. Marshall R. N., Underwood L. E., Voina S. J., Foushee D. B., Van Wyk J. J. Characterization of the insulin and somatomedin-C receptors in human placental cell membranes. J Clin Endocrinol Metab. 1974 Aug;39(2):283–292. doi: 10.1210/jcem-39-2-283. [DOI] [PubMed] [Google Scholar]
  26. Martin T. J., Findlay D. M., MacIntyre I., Eisman J. A., Michelangeli V. P., Moseley J. M., Partridge N. C. Calcitonin receptors in a cloned human breast cancer cell line (MCF 7). Biochem Biophys Res Commun. 1980 Sep 16;96(1):150–156. doi: 10.1016/0006-291x(80)91193-6. [DOI] [PubMed] [Google Scholar]
  27. Marx S. J., Aurbach G. D., Gavin J. R., 3rd, Buell D. W. Calcitonin receptors on cultured human lymphocytes. J Biol Chem. 1974 Nov 10;249(21):6812–6816. [PubMed] [Google Scholar]
  28. Marx S. J., Fedak S. A., Aurbach G. D. Preparation and characterization of a hormone-responsive renal plasma membrane fraction. J Biol Chem. 1972 Nov 10;247(21):6913–6918. [PubMed] [Google Scholar]
  29. Marx S. J., Woodward C. J., Aurbach G. D. Calcitonin receptors of kidney and bone. Science. 1972 Dec 1;178(4064):999–1001. doi: 10.1126/science.178.4064.999. [DOI] [PubMed] [Google Scholar]
  30. Marx S. J., Woodward C., Aurbach G. D., Glossmann H., Keutmann H. T. Renal receptors for calcitonin. Binding and degradation of hormone. J Biol Chem. 1973 Jul 10;248(13):4797–4802. [PubMed] [Google Scholar]
  31. Michelangeli V. P., Findlay D. M., Fletcher A., Martin T. J. Calcitonin gene-related peptide (CGRP) acts independently of calcitonin on cyclic AMP formation in clonal osteogenic sarcoma cells (UMR 106-01). Calcif Tissue Int. 1986 Jul;39(1):44–48. doi: 10.1007/BF02555739. [DOI] [PubMed] [Google Scholar]
  32. Moran J., Hunziker W., Fischer J. A. Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3984–3988. doi: 10.1073/pnas.75.8.3984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Moseley J. M., Findlay D. M., Martin T. J., Gorman J. J. Covalent cross-linking of a photoactive derivative of calcitonin to human breast cancer cell receptors. J Biol Chem. 1982 May 25;257(10):5846–5851. [PubMed] [Google Scholar]
  34. Moseley J. M., Smith P., Martin T. J. Identification of the calcitonin receptor by chemical cross-linking and photoaffinity labeling in human cancer cell lines. J Bone Miner Res. 1986 Jun;1(3):293–297. doi: 10.1002/jbmr.5650010308. [DOI] [PubMed] [Google Scholar]
  35. Nakamuta H., Furukawa S., Koida M., Yajima H., Orlowski R. C., Schlueter R. Specific binding of 125I-salmon calcitonin to rat brain: regional variation and calcitonin specificity. Jpn J Pharmacol. 1981 Feb;31(1):53–60. doi: 10.1254/jjp.31.53. [DOI] [PubMed] [Google Scholar]
  36. Nicholson G. C., Moseley J. M., Sexton P. M., Mendelsohn F. A., Martin T. J. Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest. 1986 Aug;78(2):355–360. doi: 10.1172/JCI112584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. O'Keefe E., Hollenberg M. D., Cuatrecasas P. Epidermal growth factor. Characteristics of specific binding in membranes from liver, placenta, and other target tissues. Arch Biochem Biophys. 1974 Oct;164(2):518–526. doi: 10.1016/0003-9861(74)90062-9. [DOI] [PubMed] [Google Scholar]
  38. Ramberg C. F., Jr, Delivoria-Papadopoulos M., Crandall E. D., Kronfeld D. S. Kinetic analysis of calcium transport across the placenta. J Appl Physiol. 1973 Nov;35(5):682–688. doi: 10.1152/jappl.1973.35.5.682. [DOI] [PubMed] [Google Scholar]
  39. Reynolds W. A., Pitkin R. M., Williams G. A., Bauman A. F., Hargis G. K., Beluhan F. Z., Kawahara W. Calcitonin responsiveness in the primate fetus. J Clin Endocrinol Metab. 1980 Sep;51(3):595–598. doi: 10.1210/jcem-51-3-595. [DOI] [PubMed] [Google Scholar]
  40. Rizzo A. J., Goltzman D. Calcitonin receptors in the central nervous system of the rat. Endocrinology. 1981 May;108(5):1672–1677. doi: 10.1210/endo-108-5-1672. [DOI] [PubMed] [Google Scholar]
  41. Rodbell M., Krans H. M., Pohl S. L., Birnbaumer L. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 3. Binding of glucagon: method of assay and specificity. J Biol Chem. 1971 Mar 25;246(6):1861–1871. [PubMed] [Google Scholar]
  42. Samaan N. A., Anderson G. D., Adam-Mayne M. E. Immunoreactive calcitonin in the mother, neonate, child and adult. Am J Obstet Gynecol. 1975 Mar 1;121(5):622–625. doi: 10.1016/0002-9378(75)90462-7. [DOI] [PubMed] [Google Scholar]
  43. Singer F. R., Melvin K. E., Mills B. G. Acute effects of calcitonin on osteoclasts in man. Clin Endocrinol (Oxf) 1976;5 (Suppl):333S–340S. doi: 10.1111/j.1365-2265.1976.tb03842.x. [DOI] [PubMed] [Google Scholar]
  44. Stevenson J. C., Hillyard C. J., MacIntyre I., Cooper H., Whitehead M. I. A physiological role for calcitonin: protection of the maternal skeleton. Lancet. 1979 Oct 13;2(8146):769–770. doi: 10.1016/s0140-6736(79)92117-2. [DOI] [PubMed] [Google Scholar]
  45. Takano K., Hall K., Fryklund L., Holmgren A., Sievertsson H., Uthne K. The binding of insulin and somatomedin A to human placental membrane. Acta Endocrinol (Copenh) 1975 Sep;80(1):14–31. doi: 10.1530/acta.0.0800014. [DOI] [PubMed] [Google Scholar]
  46. Warshawsky H., Goltzman D., Rouleau M. F., Bergeron J. J. Direct in vivo demonstration by radioautography of specific binding sites for calcitonin in skeletal and renal tissues of the rat. J Cell Biol. 1980 Jun;85(3):682–694. doi: 10.1083/jcb.85.3.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Whitsett J. A., Johnson C. L., Noguchi A., Darovec-Beckerman C., Costello M. Beta-Adrenergic receptors and catecholamine-sensitive adenylate cyclase of the human placenta. J Clin Endocrinol Metab. 1980 Jan;50(1):27–32. doi: 10.1210/jcem-50-1-27. [DOI] [PubMed] [Google Scholar]
  48. Zaidi M., Fuller K., Bevis P. J., GainesDas R. E., Chambers T. J., MacIntyre I. Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study. Calcif Tissue Int. 1987 Mar;40(3):149–154. doi: 10.1007/BF02555699. [DOI] [PubMed] [Google Scholar]
  49. van Buul-Offers S., Van den Brande J. L. Binding of somatomedin-A and -C, NSILA-S and insulin to human placental cell membranes. Horm Res. 1979;11(4):186–202. doi: 10.1159/000179054. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES