Radioimmunoassay of Atrial Peptide Blood and Tissue Levels

  • M. L. Michener
  • D. Schwartz
  • M. G. Currie
  • D. M. Geller
  • P. Needleman
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 82)


The observation (DeBold et al. 1981) that mammalian atria contain a peptide that is both natriuretic and diuretic has led to the discovery of a novel endocrine hormone (atriopeptin, AP) which regulates salt and water metabolism from the kidney (Needleman et al. 1985). Atrial extracts were found to be both heat and acid stable (Debold et al. 1981), and to possess spasmolytic activity on vascular smooth muscle (Currie et al. 1983). These bioassays facilitated the purification and sequence analysis of three related peptides, termed AP I, II, and III (Currie et al. 1984 a). Several peptides of different lengths, but sharing a common core sequence to the APs, have been identified by different laboratories. These include cardionatrin (Flynn et a. 1983), atrial natriuretic factor (ANF) (Thibault et al. 1983), atrial natriuretic polypeptide (ANP) (Kangawa and Matsuo 1984), and auriculin (Atlas et al. 1984). cDNA probes were constructed from the peptide sequence and used to determine the sequence for the AP gene (Yamanaka et al. 1984; Maki et al. 1984; Oikawa et al. 1984; Seidman et al. 1984). The AP gene codes for a 152 amino acid preprohormone which contains a hydrophobic 24 amino acid leader sequence (Fig. 1).


Atrial Natriuretic Peptide Atrial Pressure Atrial Natriuretic Factor Atrial Natriuretic Polypeptide Cyanogen Bromide Fragment 
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. Arendt RM, Stangl E, Zahringer J, Liebsch DC, Herz A (1985) Demonstration and char-acterization of alpha-human atrial natriuretic factor in human plasma. FEBS Lett. 189: 57–61PubMedCrossRefGoogle Scholar
  2. Atarashi K, Mulrow PJ, Franco-Saenz R, Snajdar R, Rapp J (1984) Inhibition of aldoste-rone production by an atrial extract. Science. 224: 992–994PubMedCrossRefGoogle Scholar
  3. Atlas SA, Kleinert HD, Camargo MJ, Januszewicz A, Sealey JE, Laragh JH, Schilling JW, Lewicki JA, Johnson LK, Maack T (1984) Purification, sequencing and synthesis of na¬triuretic and vasoactive rat atrial peptide. Nature. 309: 717–719PubMedCrossRefGoogle Scholar
  4. Burnett JC Jr, Granger JP, Oppenorth TJ (1984) Effects of synthetic atrial natriuretic factor on renal function and renin release. Am J PhysioL. 247: F863–F866PubMedGoogle Scholar
  5. Campbell WB, Needleman P (1985) Inhibition of aldosterone biosynthesis by atriopeptins in rat adrenal cells. Circ Res. 57: 113–118PubMedGoogle Scholar
  6. Chartier L, Schriffrin 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: 171–174PubMedCrossRefGoogle Scholar
  7. Currie MG, Neuman W (1986) Evidence for alpha-1 adrenergic receptor regulation of atriopeptin release from the isolated rat-heart. Biochem Biophys Res Commun. 137: 94–100PubMedCrossRefGoogle Scholar
  8. 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: 71–73PubMedCrossRefGoogle Scholar
  9. Currie MG, Geller DM, Cole BR, Siegel NR, Fok KF, Adams SP, Eubanks SR, Galluppi GR, Needleman P (1984 a) Purification and sequence analysis of bioactive atrial pep¬tides (atriopeptins). Science. 223: 67–69Google Scholar
  10. Currie MG, Sukin D, Geller DM, Cole BR, Needleman P (1984 b) Atriopeptin release from the isolated perfused rabbit heart. Biochem Biophys Res Commun. 124: 711–717Google Scholar
  11. Currie MG, Geller DM, Cole BR, Needleman P (1984 c) Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage. Proc Natl Acad Sei USA. 81: 1230–1233Google Scholar
  12. DeBold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sei. 28: 89–94CrossRefGoogle Scholar
  13. Dietz JR (1984) Release of natriuretic factor from heart lung preparation by atrial distension. Am J Physiol. 247: R1093–R1096PubMedGoogle Scholar
  14. 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: 859–865PubMedCrossRefGoogle Scholar
  15. Glembotski CG, Wildey GM, Gibson TR (1985) Molecular forms of immunoactive atrial natriuretic peptide in the rat hypothalamus and atrium. Biochem Biophys Res Commun. 129: 671–678PubMedCrossRefGoogle Scholar
  16. Greenberg BD, Bencen GH, Seilhamer J J, Lewicki JA, Fiddes JC (1984) Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor. Nature. 312: 656–658PubMedCrossRefGoogle Scholar
  17. Gutkowska J, Thibault G, Januszewicz P, Cantin M, Genest J (1984) Direct radioimmunoassay of atrial natriuretic factor. Biochem Biophys Res Commun. 122: 593–601PubMedCrossRefGoogle Scholar
  18. Hartter E, Weissei M, Stumm voll HK, Woloszczuk W, Punzengruber C, Ludvik B (1985) Atrial natriuretic peptide concentrations in blood from right atrium in patient with severe right heart failure. Lancet. 11: 93–94CrossRefGoogle Scholar
  19. Hintze TH, Currie MG, Needleman P (1985) Atriopeptins - renal-specific vasodilators in conscious dogs. Am J Physiol 248: H587–H591PubMedGoogle Scholar
  20. Huang C-L, Lewicki J, Johnson LK, Cogan MG (1985) Renal mechanism of action of ratatrial natriuretic factor. J Clin Invest. 75: 769–773PubMedCrossRefGoogle Scholar
  21. Kangawa K, Matsuo H (1984) Purification and complete amino acid sequence of alpha- human atrial natriuretic polypeptide (alpha-hANP). Biochem Biophys Res Commun. 118: 131–139PubMedCrossRefGoogle Scholar
  22. 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 c-DNA encoding its precursor. Nature. 312: 152–155PubMedCrossRefGoogle Scholar
  23. Kangawa K, Fukuda A, Matsuo H (1985) Structural identification of beta- and gamma-human atrial natriuretic polypeptide. Nature. 313: 397–400PubMedCrossRefGoogle Scholar
  24. Katsube N, Schwartz D, Needleman P (1985) Release of atriopeptin in the rat by vasoconstrictors or water immersion correlates with changes in right atrial pressure. Biochem Biophys Res Commun. 133: 937–944PubMedCrossRefGoogle Scholar
  25. Kawata M, Nakao K, Morii N, Kiso Y, Yamashita H, Imura H, Sano Y (1985) Atrial natriuretic polypeptide: topographical distribution in the rat brain by radioimmunoassay and immunohistochemistry. Neuroscience. 3: 521–546CrossRefGoogle Scholar
  26. Lang RE, Tholken H, Ganten D, Luft FC, Rushoaho H, Unger T (1985 a) Atrial natriuretic factor - a circulating hormone stimulated by volume loading. Nature. 314: 264–266Google Scholar
  27. Lang RE, Unger T, Ganten D, Weil J, Bidlingmaier F, Dohlemann D (1985 b) Alpha-atrial natriuretic peptide concentrations in plasma of children with congenital heart and pulmonary diseases. Br Med J. 291: 1241Google Scholar
  28. Maki M, Takayanagi R, Misono KS, Pandey KN, Tibbetts C, Inagami T (1984) Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence. Nature. 309: 722–724PubMedCrossRefGoogle Scholar
  29. Manning PT, Schwartz D, Katsube NC, Holmberg SW, Needleman P (1985) Vasopressin stimulated atriopeptin release: endocrine antagonists in fluid homeostasis. Science. 229: 395–397PubMedCrossRefGoogle Scholar
  30. McKenzie JC, Tanaka I, Misono KS, Inagami T (1985) Immunocytochemical localization of atrial natriuretic factor in the kidney, adrenal medulla, pituitary, and atrium of rat. J Histochem Cytochem 33: 828–832PubMedCrossRefGoogle Scholar
  31. Michener ML, Gierse JK, Seetharam R, Fok KF, Olins PO, Mai MS, Needleman P (1986) Proteolytic processing of atriopeptin prohormone in vivo and in vitro (to be published )Google Scholar
  32. Miyata A, Kangawa K, Toshimori T, Hatoh T, Matsuo H (1985) Molecular forms of atrial natriuretic polypeptides in mammalian tissues and plasma. Biochem Biophys Res Commun. 129: 248–255PubMedCrossRefGoogle Scholar
  33. Nakao K, Sugawara A, Morii N, Sakamoro M, Suda M, Soneda J, Ban T, Kihara M, Ya- mori Y, Shimokura M, Kiso Y, Imura H (1984) Radioimmunoassay for alpha-human and rat atrial natriuretic polypeptide. Biochem Biophys Res Commun. 124: 815–821PubMedCrossRefGoogle Scholar
  34. Nakaoka H, Imataka K, Amano M, Fuji J, Ishibashi M, Yamaji T (1985) Plasma levels of atrial natriuretic factor in patients with congestive heart failure. N Engl J Med. 313: 892–893PubMedCrossRefGoogle Scholar
  35. Nakayama K, Ohkubo H, Hirose T, Inayama S, Nakanishi S (1984) mRNA sequence for human cardiodilantin - atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature. 310: 699–701Google Scholar
  36. Needleman P, Adams SP, Cole BR, Currie MG, Geller DM, Michener ML, Saper CB, Schwartz D, Standaert DG (1985) Atriopeptins as cardiac hormones. Hypertension. 7: 469–82PubMedGoogle Scholar
  37. Nemer M, Chamberland M, Sirois D, Argentin S, Drouin J, Dixon RA, Sivin RA, Condra JH (1984) Gene structure of human cardiac hormone precursor, pronatriodilatin. Nature 312: 654–656PubMedCrossRefGoogle Scholar
  38. 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: 724–726PubMedCrossRefGoogle Scholar
  39. Rascher W, Tulassay T, Lang RE (1985) Atrial natriuretic peptide in plasma of volume-overloaded children with chronic renal failure. Lancet. 11: 303–305CrossRefGoogle Scholar
  40. Richards AM, Ikram H, Yandle TG, Nicholls MG, Webster MWI, Espiner EA (1985) Renal haemodynamic, and hormonal effects of human alpha atrial natriuretic peptide in healthy volunteers. Lancet 1: 545–548PubMedCrossRefGoogle Scholar
  41. Samson WK (1985) Atrial natriuretic factor inhibits dehydration and hemorrhage-induced vasopressin release. Neuroendocrinology 40: 277–279PubMedCrossRefGoogle Scholar
  42. Saper CB, Standaert DG, Currie MG, Schwartz D, Geller DM, Needleman P (1985) Atrio- peptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas. Science 227: 1047–1049PubMedCrossRefGoogle Scholar
  43. Schriffrin EL, Gutkowska J, Kuchel O, Cantin M, Genest J (1985) Plasma concentration of atrial natriuretic factor in a patient with paroxysmal atrial tachycardia. N Engl J Med. 312: 1196–1197CrossRefGoogle Scholar
  44. Schwartz D, Geller DM, Manning PT, Siegel NR, Fok KF, Smith CE, Needleman P (1985) Ser-Leu-Arg-Arg-Atriopeptin. III. The major circulating form of atrial peptide. Science. 229: 397–400PubMedCrossRefGoogle Scholar
  45. Seidman CE, Duby AD, Choi E, Graham RM, Haber E, Homey C, Smith JA, Seidman JG (1984) The structure of rat preproatrial natriuretic factor as defined by a complementary DNA clone. Science 225: 324–326PubMedCrossRefGoogle Scholar
  46. Shenker Y, Sider RS, Ostafin EA, Grekin RJ (1985) Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema. J Clin Invest. 76: 1684–1687PubMedCrossRefGoogle Scholar
  47. Sugawara A, Nakao K, Morii N, Sakamoto M, Suda M, Shimokura M, Kiso Y, Kihara M, Yamori Y, Nishimura K, Soneda J, Toshihiko B, Imura H (1985) Alpha-human atrial natriuretic polypeptide is released from the heart and circulates in the body. Biochem Biophys Res Commun. 129: 439–446PubMedCrossRefGoogle Scholar
  48. 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: 663–668PubMedCrossRefGoogle Scholar
  49. Thibault G, Garcia R, Seidah NG, Lazure C, Cantin M, Chretien M, Genest J (1983) Purification of three rat atrial natriuretic factors and their amino acid composition. FEBS Lett 164: 286–290PubMedCrossRefGoogle Scholar
  50. Thibault G, Lazure C, Schriffrin J, Gutkowska J, Chartier L, Garcia R, Seidah NG, Chretien M, Genest J, Cantin M (1985) Identification of a biologically active circulating form of rat atrial natriuretic factor. Biochem Biophys Res Commun. 130: 981–986PubMedCrossRefGoogle Scholar
  51. Tikkanen I, Metsarinne K, Fyhrquist F, Leidenius R (1985 a) Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet. 11: 66–69Google Scholar
  52. Tikkanen I, Metsarinne K, Fyhrquist F (1985 b) Atrial natriuretic peptide in paroxysmal supraventricular tachycardia. Lancet. 11: 40–41Google Scholar
  53. Wakitani K, Cole BR, Geller DM, Currie MG, Adams SP, Fok KF, Needleman P (1985 a) Atriopeptins - correlation between renal vasodilation and natriuresis. Am J Physiol. 249: F49–F53Google Scholar
  54. Wakitani K, Oshima T, Loewy AP, Holmberg SW, Cole BR, Adams SP, Fok KF, Currie MG, Needleman P (1985 b) Comparative vascular pharmacology of the atriopeptins. Circ Res. 56: 621–627Google Scholar
  55. Yamaji T, Ishibashi M, Takaku F (1985) Atrial natriuretic factor in human blood. J Clin Invest. 76: 1705–1709PubMedCrossRefGoogle Scholar
  56. Yamanaka M, Greenberg B, Johnson L, Seilhamer J, Brewer M, Friedemann T, Miller J, Atlas S, Laragh J, Lewicki J, Fiddes J (1984) Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor. Nature. 309: 719–722PubMedCrossRefGoogle Scholar
  57. Yukimura T, Ito Y, Takenaga T, Yamamoto K, Kangawa K, Matsuo H (1984) Renal effects of a synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) in anes¬thetized dogs. Eur J Pharmacol. 103: 363–366PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • M. L. Michener
  • D. Schwartz
  • M. G. Currie
  • D. M. Geller
  • P. Needleman

There are no affiliations available

Personalised recommendations