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Quantification of Giα-proteins in the failing and nonfailing human myocardium

  • M. Böhm
  • P. Gierschik
  • E. Erdmann

Summary

Heterotrimeric Gi-proteins play an important role in the regulation of cardiac adenylate cyclase. Besides a downregulation of β-adrenoceptors with an accompanying reduction of the positive inotropic effects of cAMP-dependent positive inotropic agents, an increase of pertussis toxin substrates (G-proteins) has been observed. The increase of G has been reported to be associated with a reduced adenylate cyclase activity in dilated cardiomyopathy from hearts with heart failure class NYHA IV. Since the quantification of G-proteins with the pertussis toxin labeling method is hampered by a number of biological and technical factors, G-proteins were quantified radioimmunologically using the iodinated C-terminus 125I-KENLKDCGLF as tracer, purified retinal transducin α as standard, and an antiserum (DS 4) raised against the same peptide. With this technique G-proteins were increased by 118% in dilated cardiomyopathy and 48% in ischemic cardiomyopathy, although pertussis toxin substrates were only increased by 40% in dilated cardiomyopathy and no change was observed in ischemic cardiomyopathy. In cardiomyopathy tissue, an inverse relationship was observed between the increase of G and the positive inotropic effects of isoprenaline or milrinone. These data provide evidence for a functional role of G in the reduced positive inotropic effects of cAMP-dependent positive inotropic agents. In addition, results obtained with pertussis toxin labeling for quantification of G-proteins do not necessarily reflect the expression of G-proteins in the human myocardium.

Key words

Heterotrimeric Gi-proteins adenylate cyclase cardiomyopathy, dilated cardiomyopathy, ischemic 

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Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co.KG, Darmstadt 1992

Authors and Affiliations

  • M. Böhm
    • 1
    • 2
  • P. Gierschik
    • 1
  • E. Erdmann
    • 1
  1. 1.Medizinische Klinik IUniversität MünchenGermany
  2. 2.Medizinische Klinik IUniversität München Klinikum GroβhadernMünchen 70Germany

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