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. 1982;1(3):297–302. doi: 10.1002/j.1460-2075.1982.tb01163.x

Parathyrin and calcitonin stimulate cyclic AMP accumulation in cultured murine brain cells.

F Löffler, D van Calker, B Hamprecht
PMCID: PMC553038  PMID: 6201357

Abstract

Despite the key role Ca2+ plays in the nervous system, biochemical actions on neural tissue of the Ca2+-regulating peptide hormones parathyrin and calcitonin were unknown. Until a few years ago only neurons, but not glial cells, were considered as targets for peptide hormones. Our recent observation that peptide hormones do indeed act on glial cells is extended by the present report that these cells respond to the calcaemic peptide hormones parathyrin and calcitonin. In cultured murine brain cells mainly consisting of glioblasts, parathyrin stimulates the accumulation of cyclic AMP. The half-maximal effect is elicited at 30 nM parathyrin. With rat brain cells the effects are three times those observed with mouse brain cells. Calcitonin, which is less potent than parathyrin, elevates the concentration of cyclic AMP only in rat brain cells. If properly occupied, the inhibitory receptors present on the cells lower the increase in the level of cyclic AMP evoked by parathyrin and, to some extent, that elicited by calcitonin. The results suggest that: (i) these or closely related hormones might exert regulatory functions in brain; and (ii) glial cells must be considered in discussions of the targets of the calcaemic and other peptide hormones.

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Selected References

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  1. Agus Z. S., Wasserstein A., Goldfarb S. PTH, calcitonin, cyclic nucleotides and the kidney. Annu Rev Physiol. 1981;43:583–595. doi: 10.1146/annurev.ph.43.030181.003055. [DOI] [PubMed] [Google Scholar]
  2. Andreatta R. H., Hartmann A., Jöhl A., Kamber B., Maier R., Riniker B., Rittel W., Sieber P. Synthese der Sequenz 1-34 von menschlichem Parat-hormon. Helv Chim Acta. 1973;56(1):470–473. doi: 10.1002/hlca.19730560139. [DOI] [PubMed] [Google Scholar]
  3. Bayliss W. M., Starling E. H. The mechanism of pancreatic secretion. J Physiol. 1902 Sep 12;28(5):325–353. doi: 10.1113/jphysiol.1902.sp000920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bialasiewicz A. A., Jüppner H., Diehl V., Hesch R. D. Binding of bovine parathyroid hormone to surface receptors of cultured B-lymphocytes. Biochim Biophys Acta. 1979 May 16;584(3):467–478. doi: 10.1016/0304-4165(79)90120-x. [DOI] [PubMed] [Google Scholar]
  5. Binet E., Evain D., Anderson W. B. Calcitonin-responsive adenylate cyclase in cultured F9 embryonal carcinoma cells. Exp Cell Res. 1980 Oct;129(2):466–469. doi: 10.1016/0014-4827(80)90516-9. [DOI] [PubMed] [Google Scholar]
  6. Bock E., Jorgensen O. S., Dittmann L., Eng L. F. Determination of brain-specific antigens in short term cultivated rat astroglial cells and in rat synaptosomes. J Neurochem. 1975 Dec;25(6):867–870. doi: 10.1111/j.1471-4159.1975.tb04419.x. [DOI] [PubMed] [Google Scholar]
  7. Bock E., Moller M., Nissen C., Sensenbrenner M. Glial fibrillary acidic protein in primary astroglial cell cultures derived from newborn rat brain. FEBS Lett. 1977 Nov 15;83(2):207–211. doi: 10.1016/0014-5793(77)81006-5. [DOI] [PubMed] [Google Scholar]
  8. Braga P., Ferri S., Santagostino A., Olgiati V. R., Pecile A. Lack of opiate receptor involvement in centrally induced calcitonin analgesia. Life Sci. 1978 Mar;22(11):971–977. doi: 10.1016/0024-3205(78)90362-4. [DOI] [PubMed] [Google Scholar]
  9. Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
  10. Brewer H. B., Jr, Ronan R. Bovine parathyroid hormone: amino acid sequence. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1862–1869. doi: 10.1073/pnas.67.4.1862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cantalamessa L., Catania A., Reschini E., Peracchi M. Inhibitory effect of calcitonin on growth hormone and insulin secretion in man. Metabolism. 1978 Aug;27(8):987–992. doi: 10.1016/0026-0495(78)90143-9. [DOI] [PubMed] [Google Scholar]
  12. Carman J. S., Wyatt R. J. Reduction of serum-prolactin after subcutaneous salmon calcitonin. Lancet. 1977 Jun 11;1(8024):1267–1268. doi: 10.1016/s0140-6736(77)92486-2. [DOI] [PubMed] [Google Scholar]
  13. Cooper C. W., Bolman R. M., 3rd, Linehan W. M., Wells S. A., Jr Interrelationships between calcium, calcemic hormones and gastrointestinal hormones. Recent Prog Horm Res. 1978;34:259–283. doi: 10.1016/b978-0-12-571134-0.50011-9. [DOI] [PubMed] [Google Scholar]
  14. Dockray G. J., Gregory R. A. Relations between neuropeptides and gut hormones. Proc R Soc Lond B Biol Sci. 1980 Oct 29;210(1178):151–164. doi: 10.1098/rspb.1980.0125. [DOI] [PubMed] [Google Scholar]
  15. Freed W. J., Perlow M. J., Wyatt R. J. Calcitonin: inhibitory effect on eating in rats. Science. 1979 Nov 16;206(4420):850–852. doi: 10.1126/science.493987. [DOI] [PubMed] [Google Scholar]
  16. Galan Galan F., Rogers R. M., Girgis S. I., MacIntyre I. Immunoreactive calcitonin in the central nervous system of the pigeon. Brain Res. 1981 May 11;212(1):59–66. doi: 10.1016/0006-8993(81)90032-9. [DOI] [PubMed] [Google Scholar]
  17. Goltzman D., Goltzmann D., Peytremann A., Callahan E., Tregear G. W., Potts J. T., Jr Analysis of the requirements for parathyroid hormone action in renal membranes with the use of inhibiting analogues. J Biol Chem. 1975 Apr 25;250(8):3199–3203. [PubMed] [Google Scholar]
  18. Hallermayer K., Harmening C., Hamprecht B. Cellular localization and regulation of glutamine synthetase in primary cultures of brain cells from newborn mice. J Neurochem. 1981 Jul;37(1):43–52. doi: 10.1111/j.1471-4159.1981.tb05289.x. [DOI] [PubMed] [Google Scholar]
  19. Iwasaki Y., Chihara K., Iwasaki J., Abe H., Fujita T. Effect of calcitonin on prolactin release in rats. Life Sci. 1979 Oct 1;25(14):1243–1248. doi: 10.1016/0024-3205(79)90467-3. [DOI] [PubMed] [Google Scholar]
  20. Katz A. I., Lindheimer M. D. Actions of hormones on the kidney. Annu Rev Physiol. 1977;39:97–133. doi: 10.1146/annurev.ph.39.030177.000525. [DOI] [PubMed] [Google Scholar]
  21. Keutmann H. T., Niall H. D., O'Riordan J. L., Potts J. T., Jr A reinvestigation of the amino-terminal sequence of human parathyroid hormone. Biochemistry. 1975 May 6;14(9):1842–1847. doi: 10.1021/bi00680a006. [DOI] [PubMed] [Google Scholar]
  22. Leicht E., Birò G., Weinges K. F. Inhibition of releasing-hormone-induced secretion of TSH and LH by calcitonin. Horm Metab Res. 1974 Sep;6(5):410–414. doi: 10.1055/s-0028-1093816. [DOI] [PubMed] [Google Scholar]
  23. Levine A. S., Morley J. E. Reduction of feeding in rats by calcitonin. Brain Res. 1981 Oct 5;222(1):187–191. doi: 10.1016/0006-8993(81)90957-4. [DOI] [PubMed] [Google Scholar]
  24. Lim R., Mitsunobu K., Li W. K. Maturation-stimulating effect of brain extract and dibutyryl cyclic AMP on dissociated embryonic brain cells in culture. Exp Eye Res. 1973 Apr;79(1):243–246. [PubMed] [Google Scholar]
  25. Luft R., Efendic S., Hökfelt T., Johansson O., Arimura A. Immunohistochemical evidence for the localization of somatostatin--like immunoreactivity in a cell population of the pancreatic islets. Med Biol. 1974 Dec;52(6):428–430. [PubMed] [Google Scholar]
  26. McCarthy K. D., de Vellis J. Alpah-adrenergic receptor modulation of beta-adrenergic, adenosine and prostaglandin E1 increased adenosine 3':5'-cyclic monophosphate levels in primary cultures of glia. J Cyclic Nucleotide Res. 1978 Feb;4(1):15–26. [PubMed] [Google Scholar]
  27. Mohr H., Hesch R. D. Different handling of parathyrin by basal-lateral and brush-border membranes of the bovine kidney cortex. Biochem J. 1980 Jun 15;188(3):649–656. doi: 10.1042/bj1880649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moonen G., Sensenbrenner M. Effects of dibutyryl cyclic AMP on cultured brain cells from chick embryos of different ages. Experientia. 1976 Jan 15;32(1):40–42. doi: 10.1007/BF01932612. [DOI] [PubMed] [Google Scholar]
  29. Morel F., Imbert-Teboul M., Chabardès D. Distribution of hormone-dependent adenylate cyclase in the nephron and its physiological significance. Annu Rev Physiol. 1981;43:569–581. doi: 10.1146/annurev.ph.43.030181.003033. [DOI] [PubMed] [Google Scholar]
  30. Mutt V., Carlquist M., Tatemoto K. Secretin-like bioactivity in extracts of porcine brain. Life Sci. 1979 Nov 12;25(20):1703–1707. doi: 10.1016/0024-3205(79)90472-7. [DOI] [PubMed] [Google Scholar]
  31. Nakhla A. M., Nandi Majumdar A. P. Calcitonin-mediated changes in plasma tryptophan and brain 5-hydroxytryptamine and acetylcholinesterase activity in rats. Biochem J. 1978 Feb 15;170(2):445–448. doi: 10.1042/bj1700445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Niall H. D., Sauer R. T., Jacobs J. W., Keutmann H. T., Segre G. V., O'Riordan J. L., Aurbach G. D., Potts J. T., Jr The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone. Proc Natl Acad Sci U S A. 1974 Feb;71(2):384–388. doi: 10.1073/pnas.71.2.384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pardridge W. M., Frank H. J., Cornford E. M., Braun L. D., Crane P. D., Oldendorf W. H. Neuropeptides and the blood-brain barrier. Adv Biochem Psychopharmacol. 1981;28:321–328. [PubMed] [Google Scholar]
  34. Parsons J. A., Erlandsen S. L., Hegre O. D., McEvoy R. C., Elde R. P. Central and peripheral localization of somatostatin. Immunoenzyme immunocytochemical studies. J Histochem Cytochem. 1976 Jul;24(7):872–882. doi: 10.1177/24.7.60436. [DOI] [PubMed] [Google Scholar]
  35. Pearse A. G., Takor T. T. Neuroendocrine embryology and the APUD concept. Clin Endocrinol (Oxf) 1976;5 (Suppl):229S–244S. doi: 10.1111/j.1365-2265.1976.tb03832.x. [DOI] [PubMed] [Google Scholar]
  36. Pecile A., Ferri S., Braga P. C., Olgiati V. R. Effects of intracerebroventricular calcitonin in the conscious rabbit. Experientia. 1975 Mar 15;31(3):332–333. doi: 10.1007/BF01922569. [DOI] [PubMed] [Google Scholar]
  37. Perlow M. J., Freed W. J., Carman J. S., Wyatt R. J. Calcitonin reduces feeding in man, monkey and rat. Pharmacol Biochem Behav. 1980 Apr;12(4):609–612. doi: 10.1016/0091-3057(80)90196-3. [DOI] [PubMed] [Google Scholar]
  38. Petralito A., Lunetta M., Liuzzo A., Mangiafico R. A., Fiore C. E. Effects of salmon calcitonin on insulin-induced growth hormone release in man. Horm Metab Res. 1979 Nov;11(11):641–643. doi: 10.1055/s-0028-1095805. [DOI] [PubMed] [Google Scholar]
  39. Potts J. T., Jr Chemistry and physiology of parathyroid hormone. Clin Endocrinol (Oxf) 1976;5 (Suppl):307S–315S. doi: 10.1111/j.1365-2265.1976.tb03839.x. [DOI] [PubMed] [Google Scholar]
  40. Propst F., Moroder L., Wünsch E., Hamprecht B. The influence of secretin, glucagon and other peptides, of amino acids, prostaglandin endoperoxide analogues and diazepam on the level of adenosine 3',5'-cyclic monophosphate in neuroblastoma x glioma hybrid cells. J Neurochem. 1979 May;32(5):1495–1500. doi: 10.1111/j.1471-4159.1979.tb11090.x. [DOI] [PubMed] [Google Scholar]
  41. Raisz L. G., Bingham P. J. Effect of hormones on bone development. Annu Rev Pharmacol. 1972;12:337–352. doi: 10.1146/annurev.pa.12.040172.002005. [DOI] [PubMed] [Google Scholar]
  42. Raisz L. G., Kream B. E. Hormonal control of skeletal growth. Annu Rev Physiol. 1981;43:225–238. doi: 10.1146/annurev.ph.43.030181.001301. [DOI] [PubMed] [Google Scholar]
  43. Robberecht P., Conlon T. P., Gardner J. D. Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate. J Biol Chem. 1976 Aug 10;251(15):4635–4639. [PubMed] [Google Scholar]
  44. Rodan S. B., Rodan G. A. Parathyroid hormone and isoproterenol stimulation of adenylate cyclase in rat osteosarcoma clonal cells. Hormone competition and site heterogeneity. Biochim Biophys Acta. 1981 Feb 18;673(1):46–54. [PubMed] [Google Scholar]
  45. Rosenblatt M., Callahan E. N., Mahaffey J. E., Pont A., Potts J. T., Jr Parathyroid hormone inhibitors. Design, synthesis, and biologic evaluation of hormone analogues. J Biol Chem. 1977 Aug 25;252(16):5847–5851. [PubMed] [Google Scholar]
  46. Sensenbrenner M., Springer N., Booher J., Mandel P. Histochemical studies during the differentiation of dissociated nerve cells cultivated in the presence of brain extracts. Neurobiology. 1972;2(2):49–60. [PubMed] [Google Scholar]
  47. Shapiro D. L. Morphological and biochemical alterations in foetal rat brain cells cultured in the presence of monobutyryl cyclic AMP. Nature. 1973 Jan 19;241(5386):203–204. doi: 10.1038/241203a0. [DOI] [PubMed] [Google Scholar]
  48. Traber J., Fischer K., Latzin S., Hamprecht B. Morphine antagonises action of prostaglandin in neuroblastoma and neuroblastoma times glioma hybrid cells. Nature. 1975 Jan 10;253(5487):120–122. doi: 10.1038/253120a0. [DOI] [PubMed] [Google Scholar]
  49. Tregear G. W., Van Rietschoten J., Greene E., Keutmann H. T., Niall H. D., Reit B., Parsons J. A., Potts J. T., Jr Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity. Endocrinology. 1973 Dec;93(6):1349–1353. doi: 10.1210/endo-93-6-1349. [DOI] [PubMed] [Google Scholar]
  50. Tregear G. W., van Rietschoten J., Greene E., Niall H. D., Keutmann H. T., Parsons J. A., O'Riordan J. L., Potts J. T., Jr Solid-phase synthesis of the biologically active N-terminal 1 - 34 peptide of human parathyroid hormone. Hoppe Seylers Z Physiol Chem. 1974 Apr;355(4):415–421. doi: 10.1515/bchm2.1974.355.1.415. [DOI] [PubMed] [Google Scholar]
  51. Van Calker D., Müller M., Hamprecht B. Adrenergic alpha- and beta-receptors expressed by the same cell type in primary culture of perinatal mouse brain. J Neurochem. 1978 Apr;30(4):713–718. doi: 10.1111/j.1471-4159.1978.tb10776.x. [DOI] [PubMed] [Google Scholar]
  52. Yamamoto M., Kumagai F., Tachikawa S., Maeno H. Lack of effect of levallorphan on analgesia induced by intraventricular application of porcine calcitonin in mice. Eur J Pharmacol. 1979 Apr 15;55(2):211–213. doi: 10.1016/0014-2999(79)90395-9. [DOI] [PubMed] [Google Scholar]
  53. van Calker D., Müller M., Hamprecht B. Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells. Nature. 1978 Dec 21;276(5690):839–841. doi: 10.1038/276839a0. [DOI] [PubMed] [Google Scholar]
  54. van Calker D., Müller M., Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem. 1979 Nov;33(5):999–1005. doi: 10.1111/j.1471-4159.1979.tb05236.x. [DOI] [PubMed] [Google Scholar]
  55. van Calker D., Müller M., Hamprecht B. Regulation by secretin, vasoactive intestinal peptide, and somatostatin of cyclic AMP accumulation in cultured brain cells. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6907–6911. doi: 10.1073/pnas.77.11.6907. [DOI] [PMC free article] [PubMed] [Google Scholar]

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