Hypertrophic responsiveness to β2-adrenoceptor stimulation on adult ventricular cardiomyocytes

  • Xi Juan Zhou
  • Klaus-Dieter Schlüter
  • Hans Michael Piper
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 19)


The aim of the present study was to characterize the receptor subtype and the second messenger involved in the newly discovered hypertrophic effect of β-adrenoeeptor stimulation in cultures of adult ventricular cardiomyocytes. Cardiomyocytes isolated from adult rats and cultured for 6 days in presence of 20% fetal calf serum (FCS) were used as experimental model. Hypertrophic responsiveness of cardiomyocytes was characterized by rate of protein synthesis, increase in protein mass, and increase in RNA content. The hypertrophic effect of the non-specific β-adrenoeeptor agonist isoprenaline was abolished in presence of a specific β2-adrenoceptor antagonist (ICI 118,551), could be mimicked by use of a β2-adrenoceptor agonist (procaterol) or direct stimulation of adenylate cyclase (forskolin) or addition of a cell-permeable analogue of cAMP (dibuytyryl-cyclo-AMP). In presence of Rp-cAMPS, an inhibitor of protein kinase A, the hypertrophic effect of isoprenaline was abolished. The results indicate that the hypertrophic effect of β-adrenoeeptor stimulation is due to stimulation of β2-adrenoceptors and activation of adenylate cyclase and protein kinase A.

Key words

adenylate cyclase protein synthesis transforming growth factor-β protein kinase A 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Morgan HE, Baker KM: Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation 83: 13–25, 1991PubMedGoogle Scholar
  2. 2.
    Bugaisky LB, Gupta M, Gupta MP, Zak R: Cellular and molecular mechnisms of cardiac hypertrophy. In: H.A. Fozzard (ed). The Heart and Cardiovascular System, 2nd edition. Raven Press, New York, 1992, pp 1621–1640Google Scholar
  3. 3.
    Fuller SJ, Gaitanaki CJ, Sugden PH: Effects of catecholamines on protein synthesis in cardiac myocytes and perfused hearts isolated from adult rats. Biochem J 266: 727–736, 1990PubMedGoogle Scholar
  4. 4.
    Schlüter K-D, Piper HM: Trophic effects of catecholamines and parathyroid hormone on adult ventricular cardiomyocytes. Am J Physiol 263:H1739–H1746, 1992PubMedGoogle Scholar
  5. 5.
    Dubus I, Samuel JL, Marotte F, Delcayre C, Rappaport L: β-Adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat hearts. Circ Res 66: 867–874, 1990PubMedGoogle Scholar
  6. 6.
    Pinson A, Schlüter K-D, Zhou XJ, Schwartz P, Kessler-Icekson G, Piper HM: Alpha- and beta-adrenergic stimulation of protein synthesis in cultured adult ventricular cardiomyocytes. J Mol Cell Cardiol 25:477–490, 1993PubMedCrossRefGoogle Scholar
  7. 7.
    Schlüter, K-D, Zhou XJ, Piper HM: Induction of hypertrophic responsiveness to β-adrenoceptor stimulation by transforming growth factor-β in adult cardiomyocytes from rats. Am J Physiol 269: C1311–C1316, 1995PubMedGoogle Scholar
  8. 8.
    Piper HM, Probst I, Schwartz P, Hütter JF, Spieckermann PG: Culturinzg of calcium stable adult cardiac myocytes. J Mol Cell Cardiol 14: 397–412, 1982PubMedCrossRefGoogle Scholar
  9. 9.
    Piper HM, Volz A, Schwartz P: Adult ventricular rat heart muscle cells. In: H.M. Piper (ed.). Cell Techniques in Heart and Vessel Research. Springer Verlag. Heidelberg, 1990, pp 158–177Google Scholar
  10. 10.
    Volz, A, Piper HM, Siegmund B, Schwartz P: Longevity of adult ventricular rat heart muscle cells in serum-free primary cultures. J Mol Cell Cardiol 23: 161–173, 1991PubMedCrossRefGoogle Scholar
  11. 11.
    Piper HM, Jacobson SL, Schwartz P: Determinants of cardiomyocyte development in long-term primary culture. J Mol Cell Cardiol 20: 825–835, 1988PubMedCrossRefGoogle Scholar
  12. 12.
    Bradford MM: A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976PubMedCrossRefGoogle Scholar
  13. 13.
    Giles KW, Myers A: An improved diphenylamine method for the estimation of deoxyribonucleic acid. Nature Lond 206: 93, 1965CrossRefGoogle Scholar
  14. 14.
    McDermott PJ, Rothblum LI, Smith SD, Morgan HE: Accelerated rates of ribosomal RNA synthesis during growth of contracting heart cells in culture. J Biol Chem 264: 18220–18227, 1989PubMedGoogle Scholar
  15. 15.
    Jacobson, SL, Piper, HM: Cell cultures of adult cardiomyocytes as models of the myocardium. J Mol Cell Cardiol 18: 661–678, 1986PubMedCrossRefGoogle Scholar
  16. 16.
    Henrich H, Piper HM, Schrader J: Evidence for cyclase coupled A1 adenosine receptors on ventricular cardiomyocytes from adult rat and dog heart. Life Sci 41: 2381–2388, 1987PubMedCrossRefGoogle Scholar
  17. 17.
    Wallenstein S, Zucker CL, Fleiss JL: Some Statistical methods useful in circulation research. Circ Res 47: 1–9, 1980PubMedGoogle Scholar
  18. 18.
    Xiao R-P, Lakattan EG: β1-Adrenoceptor stimulation and β2-adrenoceptor stimulation differ in their effects on contraction, cytosolic Ca2+, and Ca2+ current in single rat ventricular cells. Circ Res 73: 286–300, 1993PubMedGoogle Scholar
  19. 19.
    Boluyt MO, O’Neill L., Meredith, AL, Bing, OHL, Brooks WW, Conrad CH, Crow, MT, Lakatta EG: Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Circ Res 75: 23–32, 1994PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Xi Juan Zhou
    • 1
  • Klaus-Dieter Schlüter
    • 1
  • Hans Michael Piper
    • 1
  1. 1.Physiologisches InstitutJustus-Liebig-UniversitätGiessenGermany

Personalised recommendations