Dual distribution of cardiac hormones (CDD/ANP) in the heart and brain of vertebrates

  • M. Reinecke
  • D. Betzler
  • H. Segner
  • W. G. Forssmann


About four years ago, several research groups independently isolated and characterized cardiac hormones from the atrial appendages of some mammalian species. As a consequence of the different isolation procedures and the accompaning bioassays (diuresis-natriuresis, vasodilation) used, a variety of cardiac hormone candidates were presented under different names (3,7,20). However, mainly based on cDNA studies (13,17,18,28) it recently became evident that the different peptides are members of the same family and are derived from a preprohormone, which is cleaved resulting in a peptide of 126 amino acids, i.e., gamma-ANP (15) or cardiodilatin- (CDD-) 126 (8,9). This prohormone contains in its C-terminal portion the final circulating form consisting of 28 amino acids, i.e. alpha-ANP (14) which is identical to CDD-28 (99–126) (7).


Atrial Natriuretic Peptide Atrial Appendage Atrial Natriuretic Factor Specific Granule Vertebrate Classis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Back, H., Stumpf, W.E., Ando, E., Nokihara, N., Forssmann, W.G. (1986) Immuno-cytochemical evidence for CDD/ANP-like peptides in strands of myoendocrine cells associated with the ventricular conduction system of the rat heart. Anat Embryol 175: 223–336PubMedCrossRefGoogle Scholar
  2. 2.
    Bloch, K.D., Seidman, J.G., Naftilan, J.D., Fallon, J.T., Seidman, C.E. (1986) Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways. Cell 47: 695–702PubMedCrossRefGoogle Scholar
  3. 3.
    Cantin, M., Genest, J (1985) The heart and the atrial natriuretic factor. Endocr Rev 6: 107–127PubMedCrossRefGoogle Scholar
  4. 4.
    Cantin, M., Gutlkowska, J., Thibault, G., Milne, R.W., Ledoux, S., MinLi, S., Chapeau, C., Garcia, R., Hamet, P., Genest, J. (1984) Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands. Histochemistry 80: 113–127PubMedCrossRefGoogle Scholar
  5. 5.
    Chapeau, C., Gutkowska, J., Schiller, P.W., Milne, R.W., Thibault, G., Garcia, R., Genest, J., Cantin, M. (1985) Localization of immunoreactive synthetic atrial natriuretic factor (ANF) in the heart of various animal species. J Histochem Cyto-chem 33: 541–550PubMedCrossRefGoogle Scholar
  6. 6.
    DeBold, A.J., Salerno, T.A. (1983) Natriuretic activity of extracts obtained from hearts of different species and from various rat tissues. Can J Physiol Pharmacol 61: 127–130CrossRefGoogle Scholar
  7. 7.
    Forssmann, W.G. (1986) Cardiac hormones. I. Review on the morphology, biochemistry and molecular biology of the endocrine heart. Eur J Clin Invest 16: 439–451PubMedCrossRefGoogle Scholar
  8. 8.
    Forssmann, W.G., Birr, C., Carlquist, M., Christmann, M., Finke, R., Henschen, A., Hock, D., Kirchheim, H., Kreye, V., Lottspeich, F., Metz, J., Mutt, V., Reinecke, M. (1984) The auricular myocardiocytes of the heart constitute an endocrine organ. Characterization of a porcine cardiac peptide hormone, cardiodilatin-126. Cell Tissue Res 238: 425–430PubMedCrossRefGoogle Scholar
  9. 9.
    Forssmann, W.G., Hock, D., Lottspeich, F., Henschen, A., Kreye, V., Christmann, M., Reinecke, M., Metz, J., Carlquist, M., Mutt, V. (1983) The right auricle of the heart is an endocrine organ. Cardiodilatin as a peptide hormone candidate. Anat Embryol 168: 307–313PubMedCrossRefGoogle Scholar
  10. 10.
    Forssmann, W.G., Mutt, V. (1985) Cardiodilatin-immunoreactive neurons in the hypothalamus of Tupaia. Anat Embryol 172:1–5PubMedCrossRefGoogle Scholar
  11. 11.
    Forssmann, W.G., Lang, R.E., Aoki, A., Reinecke, M., Rippegather, G., Hock, D. (1987) Cardiodilatin as a neuropeptide (cardiac hormones are also neuropeptides). In: Heym, C. (ed) Histochemistry and Cell Biology of Autonomic Neurons and Paraganglia. Springer, Berlin Heidelberg New York London Paris Tokyo, pp 43–50Google Scholar
  12. 12.
    Gardner, D.G., Descheppes, C.F., Ganong, W.F., Hane, S., Fiddes, J., Baxter, J.D., Lewicki, J. (1986) Extra-atrial expression of the gene for atrial natriuretic factor. Proc Natl Acad Sci USA 83: 6697–6701PubMedCrossRefGoogle Scholar
  13. 13.
    Greenberg, B.D., Bencen, G.H., Seilhamer, J.J., Lewicki, J.A., Fiddes, J.C (1984) Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor. Nature 312: 656–658PubMedCrossRefGoogle Scholar
  14. 14.
    Kangawa, K., Matsuo, H. (1984) Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP). Biochem Biophys Res Comm 118: 131–139PubMedCrossRefGoogle Scholar
  15. 15.
    Kangawa, K., Tawaragi, Y., Oikawa, S., Mizuno, A., Sakuragawa, Y., Nakazato, H., Fukuda, A., Minamino, N., Matsuo, H. (1984) Identification of rat gamma atrial natriuretic polypeptide and characterization of the cDNA encoding its precursor. Nature 312: 152–155PubMedCrossRefGoogle Scholar
  16. 16.
    Kawata, M., Nakao, K., Morii, N., Kiso, Y., Yamashita, H., Imura, H., Sano, Y. (1985) Atrial natriuretic polypeptide: topographical distribution in the rat brain in radioimmunoassay and immunohistochemistry. Neuroscience 16: 521–546PubMedCrossRefGoogle Scholar
  17. 17.
    Maki, M., Takayanagi, R., Misono, K.S., Pandey, K.N., Tibbetts, C., Inagami, T. (1984) Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence. Nature 309: 722–724PubMedCrossRefGoogle Scholar
  18. 18.
    Nakayama, K., Ohkubo, J., Hirose, T., Inayama, S., Nakanishi, S. (1984) mRNA sequences for human cardiodilatin-atrial-natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature 310: 699–701PubMedCrossRefGoogle Scholar
  19. 19.
    Nemer, M., Lavigne, J.-P., Drouin, J., Thibault, G., Cannon, M., Antakly, T. (1986) Expression of atrial natriuretic factor gene in heart ventricular tissue. Peptides 7: 1147–1152PubMedCrossRefGoogle Scholar
  20. 20.
    Palluk, R., Gaida, W., Hoefke, W. (1985) Minireview: Atrial natriuretic factor. Life Sci 36: 1415–1425PubMedCrossRefGoogle Scholar
  21. 21.
    Reinecke, M., Nehls, M., Forssmann, W.G. (1985) Phylogenetic aspects of cardiac hormones as revealed by immunocytochemistry, electronmicroscopy and bioassay. Peptides 6 (suppl 3): 321–331PubMedCrossRefGoogle Scholar
  22. 22.
    Reinecke, M., Betzler, D., Forssmann, W.G. (1987a) Immunocytochemistry of cardiac polypeptide hormones (Cardiodilatin/atrial natriuretic polypeptide) in brain and hearts of Myxine glutinosa (Cyclostomata). Histochemistry 86: 233–239PubMedCrossRefGoogle Scholar
  23. 23.
    Reinecke, M., Betzler, D., Thorndyke, M., Forssmann, W.G., Askensten, U., Falkmer, S. (1987b) Electronmicroscopical, immunohistochemical, immunocyto-chemical and biological evidence for the occurrence of cardiac hormones (ANP/CDD) in chondrichthyes. Histochemistry 87: 531–538PubMedCrossRefGoogle Scholar
  24. 24.
    Saper, C.B., Standaert, D.G., Currie, M.G., Schwartz, D., Geller, D.M., Needleman, P. (1985) Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas. Science 227: 1047–1049PubMedCrossRefGoogle Scholar
  25. 25.
    Skofitsch, G., Jacobowitz, D.M., Eskay, R.L., Zamir, N. (1985) Distribution of atrial natriuretic factor-like immunoreactive neurons in the rat brain. Neuroscience 16: 917–948PubMedCrossRefGoogle Scholar
  26. 26.
    Toshimori, H., Toshimori, K., Oura, C., Matsuo, H. (1987) Immunohistochemistry and immunocytochemistry of atrial natriuretic polypeptide in porcine heart. Histochemistry 86: 595–601PubMedCrossRefGoogle Scholar
  27. 27.
    Zamir, N., Skofitsch, G., Eskay, R.L., Jacobowitz, D.M. (1985) Distribution of immunoreactive atrial natriuretic peptides in the central nervous system of the rat. Brain Res 365: 105–111CrossRefGoogle Scholar
  28. 28.
    Zivin, R.A., Condra, J.H., Dixon, R.A.F., Seidah, N.G., Chrétien, M., Nemer, M., Chamberland, M., Drouin, J. (1984) Molecular cloning and characterization of DNA sequences encoding rat and human atrial natriuretic factors. Proc Natl Acad Sci USA 81: 6325–6329PubMedCrossRefGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1989

Authors and Affiliations

  • M. Reinecke
    • 1
  • D. Betzler
    • 1
  • H. Segner
    • 1
  • W. G. Forssmann
    • 1
  1. 1.Department of Anatomy and Cell BiologyUniversity of HeidelbergHeidelbergGermany

Personalised recommendations