Skip to main content
Log in

Physiological effects and biochemical properties of a serum protein that produces positive inotropic and chronotropic effects on isolated guinea pig atria

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Isolated left and right guinea pig atria were used as a bioassay for the detection of an endogenous cardioactive substance in bovine serum. Serum, buffer exchanged to Krebs–Henseleit solution, produced positive inotropic and chronotropic effects on the isolated guinea pig atria. The cardiotonic effects were unaffected by the combined presence of propranolol and methysergide (both 10−6M) and were also dissimilar in time course from other known cardiotons such as catecholamines and cardiac glycosides. Following ultrafiltration (using XM100A Amicon membranes), activity was found solely in the retentate fractions and was therefore probably due to a large molecular weight (>100 kDa) substance or a small molecule bound to a large protein. The cardioactive factor (CF) in the whole serum was heat labile, sensitive to acidification, exposure to potassium bromide and equilibration to physiological buffers of a low ionic strength. Isolation by conventional protein purification techniques was unsuccessful due to the labile nature of the active molecule(s) when exposed to non-physiological experimental conditions. Physical and biochemical properties of the CF which may help avoid inactivation are discussed for future experiments aimed at elucidating the nature and identity of the cardiotonic principle. (Mol Cell Biochem 261: 201–207, 2004)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bowditch H: Uber die weigenthumlickeoten der reizbarkeit, welche die muskelfassern des hezens ziegen. Arbeiten aus der physiol. Anstalt zu leipzig 6: 139–176, 1871

    Google Scholar 

  2. Ringer S: Regarding the influence of the organic constituents of blood on the contractility of the ventricle. J Physiol 6: 361–381, 1985

    Google Scholar 

  3. Clark AJ: The action of ions and lipoids on the frog's heart. J Physiol (Lond) 47: 66–107, 1913

    Google Scholar 

  4. Hajdu S, Szent-Gyorgi A: Actions of DOC and serum on the frog heart. Am J Physiol 168: 159–170, 1952

    CAS  PubMed  Google Scholar 

  5. Hajdu S: Bioassay for cardiac active principles based on the staircase phenomenon of the frog heart. J Pharmacol Exp Ther 120: 90–98, 1957

    CAS  PubMed  Google Scholar 

  6. Szent-Gyorgi A: In: Chemical Physiology of Contraction in Body and Heart Muscle. Academic Press, New York, p 88, 1953

    Google Scholar 

  7. Gruber K, Whittaker J, Wardman MJ: Endogenous digitalis?like substances in plasma of volume expanded dogs. Nature 187: 743–746, 1980

    Google Scholar 

  8. Hamlyn J, Schenden J, Zyren J, Backzynsky L: Purification and characterisation of digitalis-like factors from human plasma. Hypertension 10: I-71–I-77, 1987

    CAS  Google Scholar 

  9. Hajdu S, Leonard EJ, Akers RP: Action of human plasma on the isolated frog heart. Observations on patients with and without essential hypertension. Circ Res 5: 319–322, 1957

    CAS  PubMed  Google Scholar 

  10. Hajdu S, Leonard EJ: A human serum protein system affecting muscle contractility: Characterisation of the five components and their reaction sequence. J Cell Physiol 96: 279–290, 1978

    Article  CAS  PubMed  Google Scholar 

  11. Nayler WG, McCulloch M: The positive inotropic activity of plasma. Aust J Exp Biol Med Sci 38: 127–134, 1960

    CAS  PubMed  Google Scholar 

  12. Curtain CC, Nayler WG: The isolation from human blood plasma of a substance having positive inotropic action on the isolated toad heart. Biochem J 89: 69–75, 1963

    CAS  PubMed  Google Scholar 

  13. Hakim A: Alteration of cAMP action on ATP induced muscular contraction by a serum enzyme. Experentia 27: 883–885, 1971

    Article  CAS  Google Scholar 

  14. Hakim A: Action of a serum protein on muscular contraction. Pflugers Arch 338: 133–157, 1973

    Article  CAS  PubMed  Google Scholar 

  15. Kalman SM, Jones RMA: Cardioactive factor in human plasma with positive inotropic and positive chronotropic activities. Proc Natl Acad Sci USA 77: 6820–6821, 1980

    CAS  Google Scholar 

  16. Hajdu S, Leonard EJ: Cardioglobulin-Assay methods. Circ Res 9: 881–890, 1961

    CAS  Google Scholar 

  17. Hajdu S, Leonard EJ: Binding of cardioglobulin C-calcium 45 to cardiac muscle and release by cardioglobulin A. Am J Physiol 209: 1–7, 1965

    CAS  PubMed  Google Scholar 

  18. Leonard EJ, Hajdu S: Protection and reactivation of cardioglobulin?A by high energy phosphate compounds. Circ Res 15: 506–413, 1964

    Google Scholar 

  19. Dorevitch N, Nayler WG, Lowe TE: The action on isolated smooth muscle of kinekard, a cardioactive fraction from human plasma. J Pharmacol Exp Ther 155: 367–375, 1967

    CAS  PubMed  Google Scholar 

  20. Masiar E, Masiar P: Trace peptides with positive inotropic action in blood plasma of dogs. 1. Chemistry and physiological significance of the peptide constituents of an intermediate molecular weight (1,000-10,000 daltons) peptide fraction from heparinised dog plasma. Comp Biochem Physiol 49A: 65–80, 1974

    Google Scholar 

  21. Singh J, Hutton T, Hussain M, Waring JJ: Effects of serum, its protein and lipid extracts, and commercial serum proteins and lipid on the isolated frog heart. J Comp Physiol B 161: 303–310, 1991

    Article  CAS  PubMed  Google Scholar 

  22. Green JP, Nahum CH: The actions of serum protein fractions on myocardial contractility. Circ Res 5: 634–640, 1957

    CAS  PubMed  Google Scholar 

  23. Haddy F, Pamnani M: Evidence for a circulating endogenous sodium Na+, K+ pump inhibitor in low renin hypertension. Fed Proc 44: 2789–2794, 1985

    CAS  PubMed  Google Scholar 

  24. Goetz K: Physiology and pathophysiology of atrial peptides. Am J Physiol 254: E1–E15, 1988

    CAS  PubMed  Google Scholar 

  25. Tripodo N: An update on the physiology of atrial natriuretic factor. Hypertension 10: I-122–I-127, 1987

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hussain, M., Chorvatova, A. & Singh, J. Physiological effects and biochemical properties of a serum protein that produces positive inotropic and chronotropic effects on isolated guinea pig atria. Mol Cell Biochem 261, 201–207 (2004). https://doi.org/10.1023/B:MCBI.0000028757.98334.5a

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000028757.98334.5a

Navigation