Interaction of β-adrenoceptor and adenosine receptor agonists on phosphorylation. Identification of target proteins in mammalian ventricles

J. Neumann, R. C. Gupta, L. R. Jones, G. S. Bodor, S. Bartel, E. G. Krause, H. T. Pask, W. Schmitz, H. Scholz, A. M. Watanabe

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The influence of the adenosine derivatives (-)-N6-phenylisopropyladenosine (R-PIA, 1 μm) and 5′-N-ethylcarbox-amidoadenosine (NECA, 1 μm) on β-adrenergic stimulated (isoproterenol, 10 nm) phosphorylation of sarcolemmal (15 kDa protein), sarcoplasmic reticular (phospholamban) and myofibrillar proteins (troponin I. C-protein) was studied in isolated 32P-labeled guinea-pig ventricles. The identification of the 15 kDa protein, phospholamban, troponin I and C-protein was based on their reaction with specific antibodies. Isoproterenol increased contractile parameters (developed tension, rate of tension development, rate of relaxation) and stimulated the phosphorylation state of a 15 kDa protein (now named phospholemman), of phospholamban, troponin I and C-protein (regarded as regulatory proteins). Isoproterenol concomitantly increased myocardial cyclic AMP levels. R-PIA and NECA attenuated the effects of isoproterenol on contractile parameters as well as on the phosphorylation of the regulatory proteins without affecting cyclic AMP levels. The effects of 1 μm R-PIA and 1 μm NECA on the isoproterenol-stimulated phosporylation of regulatory proteins were blocked by the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1 μm). Therefore, it is concluded that adenosine derivatives acting via adenosine receptors can reduce the isoproterenol-stimulated phosphorylation state of the following regulatory proteins: phospholemman, phospholamban, troponin I and C-protein.

Original languageEnglish (US)
Pages (from-to)1655-1667
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number8
DOIs
StatePublished - Aug 1995

Keywords

  • Adenosine
  • C-protein
  • Phospholamban
  • Phospholemman
  • Troponin I

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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