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Das Herz, ein endokrines Organ: Die Entdeckung eines neuen Hormons

The heart is an endocrine gland: Discovery of a new hormone

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Summary

Ever since the early work of Henry and Gauer (1956) it has been clear that a link exists between the atria of mammals and diuresis. In 1981, De Bold et al. described that atrial extracts, injected intravenously into rats, caused diuresis. The hormone responsible for this diuresis has quickly been identified. The peptide hormone, atrial natriuretic factor (ANF), which is also known as atrial natriuretic peptide(s) (ANP), cardionatrin, cardiodilatin, atrin or auriculin, has been sequenced and synthetically produced. Its genomic DNA has been cloned. ANF raises cyclic GMP in target cells and activates particulate guanylate cyclase but not soluble guanylate cyclase. So far, no other hormone has conclusively been shown to activate particulate guanylate cyclase. ANF is formed and secreted in the atria but not in the ventricles of mammals, including man. The action of ANF involves natriuresis, vasorelaxation and inhibition of aldosterone secretion. ANF or ANF derivatives may represent a therapeutically useful new class of agents.

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Abbreviations

ANF:

atrialer natriuretischer Faktor

cAMP:

zyklisches 3′,5′-Adenosinmonophosphat

cGMP:

zyklisches 3′,5′-Guanosinmonophosphat

Literatur

  1. Anand-Srivastava MB, Franks DJ, Cantin M, Genest J (1984) Atrial natriuretic factor inhibits adenylate cyclase activity. Biochem Biophys Res Commun 121:855–862

    Google Scholar 

  2. Arndt JO, Reineck H, Gauer OH (1963) Ausscheidungs-funktion und Hämodynamik der Nieren bei Dehnung des linken Vorhofs am narkotisierten Hund. Arch Ges Physiol 277:1–15

    Google Scholar 

  3. Atarashi K, Mulrow PJ, Franco-Saenz R, Snajdar R, Rapp J (1984) Inhibition of aldosterone production by an atrial extract. Science 224:992–994

    Google Scholar 

  4. Atlas SA, Kleinert HD, Camargo MJ, Januszewicz A, Sealey JE, Laragh JH, Schilling JW, Lewicki JA, Johnson LK, Maak T (1984) Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide. Nature 309:717–719

    Google Scholar 

  5. Baines AD, DeBold AJ, Sonnenberg H (1983) Natriuretic effect of atrial extract on isolated perfused rat kidney. Can J Physiol Pharmacol 61:1462–1466

    Google Scholar 

  6. Böhme E, Graf H, Schultz G (1978) Effects of sodium nitroprusside and other smooth muscle relaxants on cyclic GMP formation in smooth muscle and platelets. Adv Cyclic Nucl Res 9:131–143

    Google Scholar 

  7. Böhme E, Grossmann G, Spies C (1984) Stimulierung der cGMP-Bildung durch Molsidomin und organische Nitrate. Med Prax (Sondernummer 1):18–23

  8. Briggs JP, Steipe B, Schubert G, Schnermann J (1982) Micropuncture studies of the renal effects of atrial natriuretic substance. Pflüger's Arch 395:271–276

    Google Scholar 

  9. Briggs JP, Marin-Grez M, Steipe B, Schubert G, Schnermann J (1984) Inactivation of atrial natriuretic substance by kallikrein. Amer J Physiol 247:F480-F484

    Google Scholar 

  10. Brunton TL (1857) Use of nitrite of amyl in angina pectoris. Lancet II:97–98, 561–564

    Google Scholar 

  11. Camargo MJ, Kleinert HD, Atlas SA, Sealey JE, Laragh JH, Maak T (1984) Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Amer J Physiol 246:F447–456

    Google Scholar 

  12. Cantin M, Gutkowska J, Thibault G, Milne RW, Ledoux S, MinLi S, Chapeau C, Garcia R, Hamet P, Genest J (1984a) Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands. Histochem 80:113–127

    Google Scholar 

  13. Cantin M, Gutkowska J, Thibault G, Garcia R, Anand-Srivastava M, Hamet P, Schiffrin E, Genest J (1984b) The heart is an endocrine gland. In: Labrie F, Proulx L (eds), Endocrinology. Elsevier 684–689

  14. Chartier L, Schiffrin E, Thibault G (1984) Effect of atrial natriuretic factor (ANF)-related peptides on aldosterone secretion by adrenal glomerulosa cells: Critical role of the intramolecular disulphide bond. Biochem Biophys Res Commun 122:171–174

    Google Scholar 

  15. Chimoskey JE, Spielman WS, Brandt MA, Heidemann SR (1984) Cardiac atria of BIO 14.6 hamsters are deficient in natriuretic factor. Science 223:820–821

    Google Scholar 

  16. Currie MG, Geller DM, Cole BR, Boylan JG, YuSheng W, Holmberg SW, Needleman P (1983) Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. Science 221:71–73

    Google Scholar 

  17. Currie MG, Geller DM, Cole BR, Siegel NR, Fok KF, Adams SP, Eubanks SR, Gallupi GR, Needleman P (1984a) Purification and sequence analysis of bioactive atrial peptides (atriopeptins). Science 223:67–69

    Google Scholar 

  18. Currie MG, Geller DM, Cole BR, Needleman P (1984b) Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage. Proc Natl Sci Acad USA 81:1230–1233

    Google Scholar 

  19. De Bold AJ (1979) Heart atria granularity effects changes in water-electrolyte balance. Proc Soc Exper Med 161:508–512

    Google Scholar 

  20. De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 28:89–94

    Google Scholar 

  21. De Lean A, Racz K, Gutkowska J, Nguyen T-T, Cantin M, Genest J (1983a) Specific receptor-mediated inhibition by synthetic atrial natriuretic factor of hormone-stimulated steroidogenesis in cultured bovine adrenal cells. Endocrinology 115:1636–1638

    Google Scholar 

  22. De Lean A, Gutkowska J, McNicoll N, Schiller PW, Cantin M, Genest J (1984b) Characterization of specific receptors for atrial natriuretic factor in bovine adrenal zona glomerulosa. Life Sci 35:2311–2318

    Google Scholar 

  23. De Wardener HE, Clarkson EM (1982) The natriuretic hormone: Recent developments. Clin Sci 63:415–420

    Google Scholar 

  24. Field M, Graf LH, Laird WJ, Smith PL (1978) Heat-stable enterotoxin of Escherichia Coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci USA 75:2800–2804

    Google Scholar 

  25. Fitzgerald DJ, Roy L, Robertson RM, Fitzgerald GA (1984) The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans. Circulation 70:297–302

    Google Scholar 

  26. Flynn TG, DeBold ML, DeBold AJ (1983) The amino acid sequence of an atrial peptide with potent diuretic and natriuretic properties. Biochem Biophys Res Commun 117:859–865

    Google Scholar 

  27. Gauer OH, Henry JP (1963) Circulatory basis of fluid volume control. Physiol Rev 43:423–481

    Google Scholar 

  28. Genest J (1983) Volume hormones and blood pressure. Ann Intern Med 98:744–749

    Google Scholar 

  29. Gerzer R, Hofmann F, Schultz G (1981a) Purification of a soluble, sodium nitroprusside-stimulated guanylate cyclase from bovine lung. Eur J Biochem 116:479–486

    Google Scholar 

  30. Gerzer R, Böhme E, Hofmann F, Schultz G (1981b) Soluble guanylate cyclase purified from bovine lung contains heme and copper. FEBS Lett 132:71–74

    Google Scholar 

  31. Gerzer R, Radany EW, Garbers DL (1982) The separation of the heme and apoheme forms of soluble guanylate cyclase. Biochem Biophys Res Commun 108:678–686

    Google Scholar 

  32. Gerzer R, Hamet P, Ross AH, Lawson JA, Hardman JG (1983) Ca++-induced release from platelet membranes of fatty acids that modulate soluble guanylate cyclase. J Pharmacol Exp Ther 226:180–186

    Google Scholar 

  33. Gerzer R, Tremblay J, Pang SC, DeLean A, Hamet P (1985a) Atrial natriuretic factor activates mammalian particulate guanylate cyclase. Fed Proc 44:698

    Google Scholar 

  34. Gerzer R, Tremblay J, Pang SC, Vinay P, Cantin M, Genest J, Hamet P (1985b) Atrial natriuretic factor activates particulate guanylate cyclase in specific target cells. (submitted)

  35. Grantham JJ, Edwards RM (1984) Natriuretic hormones: At least, bottled in bond? Editorial. J Lab Clin Med 103:333–336

    Google Scholar 

  36. Gruber KA, Whitaker JM, Buckalew VM Jr. (1980) Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature 287:743–745

    Google Scholar 

  37. Gutkowska J, Thibault G, Milne RW, Januszewicz P, Schiller PW, Cantin M, Genest J (1984) Radioimmunoassay of atrial natriuretic factor (ANF) in rat atria. Proc Soc Exp Biol Med 176:105–108

    Google Scholar 

  38. Hamet P, Tremblay J, Thibault G, Garcia R, Cantin M, Genest J (1983) Effect of atrial natriuretic factor on metabolism of cyclic GMP. The Endocrine Society 65:289

    Google Scholar 

  39. Hamet P, Tremblay J, Pang SC, Garcia R, Thibault G, Gutkowska J, Cantin M, Genest J (1984) Effect of native and synthetic atrial natriuretic factor on cyclic GMP. Biochem Biophys Res Commun 123:515–527

    Google Scholar 

  40. Harris RB, Wilson IB (1984) Atrial tissue contains a metallo dipeptidyl carboxyhydrolase not present in ventricular tissue: partial purification and characterization. Arch Biochem Biophys 233:667–675

    Google Scholar 

  41. Henry JP, Gauer OH, Reeves JL (1956) Evidence of the atrial location of receptors influencing urine flow. Circulation Res 4:85

    Google Scholar 

  42. Hirata Y, Tomita M, Yoshimi H, Ikeda M (1984) Specific receptors for atrial natriuretic factor (ANF) in cultured vascular smooth muscle cells of rat aorta. Biochem Biophys Res Commun 125:562–568

    Google Scholar 

  43. Huet M, Cantin M (1974) Ultrastructural cytochemistry of atrial muscle cells. II. Characterization of the protein content of specific granules. Lab Invest 30:525–532

    Google Scholar 

  44. Hughes JM, Murad F, Chang B, Guerrant RL (1978) Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia Coli. Nature 271:755–756

    Google Scholar 

  45. Kaczmarczyk G, Christe W, Mohnhaupt R, Reinhardt HW (1983) An attempt to quantitate the contribution of antidiuretic hormone to the diuresis of left atrial distension in conscious dogs. Pflügers Arch 396:101–105

    Google Scholar 

  46. Keeler R (1982) Atrial natriuretic factor has a direct, prostaglandin-independent action on kidneys. Can J Physiol Pharmacol 60:1078–1082

    Google Scholar 

  47. Kennedy BP, Marsden JJ, Flynn TG, DeBold AJ, Davies PL (1984) Isolation and nucleotide sequence of a cloned cardionatrin cDNA. Biochem Biophys Res Commun 122:1076–1082

    Google Scholar 

  48. Kisch B (1956) Electron microscopy of the atria of the heart. I. Guinea pig. Exp Med Surg 14:99–112

    Google Scholar 

  49. Kleinert HD, Maack T, Atlas SA, Januszewicz A, Sealey JE, Laragh JH (1984) Atrial natriuretic factor inhibits angiotensin-, norepinephrine-, and potassium-induced vascular contractility. Hypertension 6 (suppl 1):143–147

    Google Scholar 

  50. Kramer HJ, Glänzer K, Freitag T, Schönfeld J, Sorger M, Schlebusch H, Düsing R, Krück F (1985) Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Klin Wochenschr 63:32–36

    Google Scholar 

  51. Kudo T, Baird A (1984) Inhibition of aldosterone production in the adrenal glomerulosa by atrial natriuretic factor. Nature 312:756–757

    Google Scholar 

  52. Lancet (1984) Editorial: Atrial natriuretic peptides 8398:328–329

    Google Scholar 

  53. Levin RI, Jaffe EA, Weksler BB, Tack-Goldmann K (1981) Nitroglycerin stimulates synthesis of prostacyclin by cultured human endothelial cells. J Clin Invest 67:762–769

    Google Scholar 

  54. Lincoln TM, Fisher-Simpson V (1983) A comparison of the effects of forskolin and nitroprusside on cyclic nucleotides and relaxation in the rat aorta. Eur J Pharmacol 101:17–27

    Google Scholar 

  55. Maak T, Marion DN, Camargo MJF, Kleinert HD, Laragh JH, Vaughan ED, Atlas SA (1984) Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs. Amer J Med 77:1069–1075

    Google Scholar 

  56. Maki M, Takayanagi R, Misono KS, Pandey KN, Tibbetts C, Inagami T (1984a) Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence. Nature 309:722–724

    Google Scholar 

  57. Maki M, Parmentier M, Inagami T (1984b) Cloning of genomic DNA for human atrial natriuretic factor. Biochem. Biophys Res Commun 125:797–802

    Google Scholar 

  58. Mills IH (1984) Atrial natriuretic factor: a new hormone? Brit Med J 289:210–211

    Google Scholar 

  59. Misono KS, Fukumi H, Grammer RT, Inagami T (1984) Rat atrial natriuretic factor: complete amino acid sequence and disulfide linkage essential for biological activity. Biochem Biophys Res Commun 119:524–529

    Google Scholar 

  60. Nakayama K, Ohkubo H, Hirose T, Inayama S, Nakanishi S (1984) mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature 310:699–701

    Google Scholar 

  61. Needleman P, Currie MG, Geller DM, Cole BR, Adams SP (1984) Atriopeptins: potential mediators of an endocrine relationship between heart and kidney. TIPS 5:506–509

    Google Scholar 

  62. Ohlstein EH, Sherman SS, Berkowitz BA (1984) Fed Proc 78:99A

  63. Oikawa S, Imai M, Ueno A, Tanaka S, Noguchi T, Nakazato H, Kangawa K, Fukuda A, Matsuo H (1984) Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide. Nature 309:722–724

    Google Scholar 

  64. Osswald H (1974) Cyclic guanosine-3′:5′-monophosphate induced diuresis in rats. Naunyn-Schmiedeberg's Arch Pharmacol 284:207–214

    Google Scholar 

  65. Pollock DM, Mullins MM, Banks RO (1983) Failure of atrial myocardial extract to inhibit renal Na+,K+-ATPase. Renal Physiol 6:295–299

    Google Scholar 

  66. Pollock DM, Banks RO (1984) Influence of dietary sodium on the natriuretic activity of atrial tissue. Mineral Electrolyte Metab 10:337–342

    Google Scholar 

  67. Radany EW, Gerzer R, Garbers DL (1983) Purification and characterization of particulate guanylate cyclase from sea urchin spermatozoa. J Biol Chem 258:8346–8351

    Google Scholar 

  68. Rapoport RM, Draznin MB, Murad F (1983) Endotheliumdependent vasodilator- and nitrovasodilator- induced relaxation may be mediated through cyclic GMP formation and cyclic GMP-dependent protein phosphorylation. Trans Assoc Amer Physicians 96:19–30

    Google Scholar 

  69. Saper CB, Standaert DG, Currie MG, Schwartz D, Geller DM, Needleman P (1985) Atriopeptin-immunoreactive neurons in the brain: Presence in cardiovascular regulatory areas. Science 227:1047–1049

    Google Scholar 

  70. Schultz G, Hardman JG, Schultz K, Baird CE, Sutherland EW (1973) The importance of calcium ions for the regulation of guanosine 3′,5′-cyclic monophosphate levels. Proc Natl Acad Sci USA 70:3889–3893

    Google Scholar 

  71. Schultz G, Aktories K, Böhme E, Gerzer R, Jakobs KH (1982) Signal transformation mediated by membrane receptors for hormones and neurotransmitters. Molecul Immunol 19:1207–1214

    Google Scholar 

  72. Seidah NG, Lazure C, Chretien M, Thibault G, Garcia R, Cantin M, Genest J, Nutt RF, Brady SF, Lyle TA, Paleveda WJ, Colton CD, Ciccarone TM, Veber DF (1984) Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms. Proc Natl Acad Sci USA 81:2640–2644

    Google Scholar 

  73. Sonnenberg H, Cupples WA, De Bold AJ, Veress AT (1982) Intrarenal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol 60:1149–1152

    Google Scholar 

  74. Sonnenberg H, Milojevic S, Chong CK, Veress AT (1983) Atrial natriuretic factor: reduced cardiac content in spontaneously hypertensive rats. Hypertension 5:672–675

    Google Scholar 

  75. Sonnenberg H, Veress AT (1984) Cellular mechanism of release of atrial natriuretic factor. Biochem Biophys Res Commun 124:443–449

    Google Scholar 

  76. Suzuki N, Shimomura H, Radany EW, Ramarao CS, Ward GE, Bentley JK, Garbers DL (1984) A peptide associated with eggs causes a mobility shift in a major plasma membrane protein of spermatozoa. J Biol Chem 259:14874–14879

    Google Scholar 

  77. Tanaka I, Misono KS, Inagami T (1984) Atrial natriuretic factor in rat hypothalamus, atria and plasma: Determination by specific radioimmunoassay. Biochem Biophys Res Commun 124:663–668

    Google Scholar 

  78. Thibault G, Garcia R, Cantin M, Genest J (1983) Atrial natriuretic factor. Characterization and partial purification. Hypertension 5 (suppl 1) 75–80

    Google Scholar 

  79. Thibault G, Garcia G, Carrier F, Seidah NG, Lazure C, Chretien M, Cantin M, Genest J (1984) Structure-activity relationships of atrial natriuretic factor (ANF). I. Natriuretic activity and relaxation of intestinal smooth muscle. Biochem Biophys Res Commun 125:938–946

    Google Scholar 

  80. Tremblay J, Gerzer R, Vinay P, Pang SC, Beliveau R, Hamet P (1985) The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanaylate cyclase. FEBS Lett 181:17–22

    Google Scholar 

  81. Turner AJ (1985) Hormones from the heart. TIBS 10:2–3

    Google Scholar 

  82. Van Dommelen FS, DeJonge HR (1984) Cyclic GMP- and cyclic AMP-induced intestinal ion secretion: analysis at the level of brush border membrane vesicles. Adv Cyclic Nucl Prot Phos Res 17:303–313

    Google Scholar 

  83. Vesely DL (1984) Cation-dependent prolactin activation of guanylate cyclase. Biochem Biophys Res Commun 123:1084–1090

    Google Scholar 

  84. Waldman SA, Rapoport RM, Murad F (1984) Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 259:14332–14334

    Google Scholar 

  85. Winquist RJ, Faison EP, Waldman SA, Schwartz K, Murad F, Rapoport RM (1984) Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci USA 81:7661–7664

    Google Scholar 

  86. Yamanaka M, Greenberg B, Johnson L, Seilhamer J, Brewer M, Friedemann T, Miller J, Atlas S, Laragh J, Lewicki J (1984) Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor. Nature 309:719–722

    Google Scholar 

  87. Yukimura T, Ito K, Takenaga T, Yamamoto K, Kangawa K, Matsuo H (1984) Renal effects of synthetic a-human atrial natriuretic polypeptide (a-hANP) in anesthetized dogs. Eur J Pharmacol 103:363–366

    Google Scholar 

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Gerzer, R. Das Herz, ein endokrines Organ: Die Entdeckung eines neuen Hormons. Klin Wochenschr 63, 529–536 (1985). https://doi.org/10.1007/BF01733196

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