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Modulation of the beta-adrenergic-response in cultured rat heart cells

II. Mammary-derived growth inhibitor (MDGI) blocks induction of beta-adrenergic supersensitivity. Dissociation from lipid-binding activity of MDGI

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Summary

‘Mammary-derived growth inhibitor (MDGI)’ is a 14.5 kDa polypeptide with growth-inhibitory activity for various mammary epithelial cells in vitro which is highly homologous to cardiac fatty acid-binding protein (H-FABP). Here we describe a new biological activity of MDGI: Inhibition of L(+)-lactate-, arachidonic acid- and 15-S-hydroxyeicosatetraenoic acid-induced supersensitivity of neonatal rat heart cells for beta-adrenergic stimulation, concerning particularly a small population of beta2 receptors. Synthetic peptides corresponding to the MDGI-sequence, residue 121–131 mimic the effect of MDGI. Measurements of lipid-binding to MDGI and synthetic peptides excluded the binding of arachidonic acid, 15-S-hydroxyeicosatetraenoic acid or beta-adrenergic agonists to MDGI or the peptides as the mechanism for this effect. Also, no direct interference of MDGI and the synthetic peptides with the binding of the beta-adrenergic agent CGP 12177 to its receptor on A431 cells could be detected.

We suggest that MDGI and the peptides act by interference with the function of the beta2-adrenergic receptor and that this mechanism might also be relevant for the growth-inhibitory activity of MDGI. Furthermore, the data point to a possible function of H-FABP for the modulation of beta-adrenergic sensitivity of cardiac myocytes.

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Abbreviations

MDGI:

mammary-derived growth inhibitor

HETE:

hydroxyeicosatetraenoic acid

CGP 12177:

((+/-)-4-(3-t-butylamino-2-hydroxypropoxy)-benzimidazole-2-one

PBS:

phosphate buffered saline: 20 mM sodium phosphate, 150 mM sodium chloride, pH 7.4

HEPES:

N-(2-hydroxyethyl)piperazine-N′-2-ethanesulfonic acid

SDS:

sodium dodecylsulfate

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Authors and Affiliations

  1. Central Institute for Cardiovascular Research, Central Institute of Molecular Biology, Academy of Sciences, 1115, Berlin-Buch, Germany

    Gerd Wallukat

  2. Departments of Cell Biology, Central Institute of Molecular Biology, Academy of Sciences, 1115, Berlin-Buch, Germany

    Frank-D. Boehmer, Peter Langen & Richard Grosse

  3. Molecular Biophysics, Central Institute of Molecular Biology, Academy of Sciences, 1115, Berlin-Buch, Germany

    Joachim Behlke

  4. Ludwig Institute for Cancer Research, Uppsala Branch, 75321, Uppsala, Sweden

    Ulla Engstroem

  5. Department of Pharmacology and Therapeutics, University of Calgary, T2N 4N1, Calgary, Canada

    Morley Hollenberg

  6. Institute for Biochemistry, Humboldt-Universitaet Berlin, Berlin, Germany

    Hartmut Kuehn

Authors
  1. Gerd Wallukat
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  2. Frank-D. Boehmer
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  3. Ulla Engstroem
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  4. Peter Langen
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  5. Morley Hollenberg
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  6. Joachim Behlke
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  7. Hartmut Kuehn
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  8. Richard Grosse
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Wallukat, G., Boehmer, FD., Engstroem, U. et al. Modulation of the beta-adrenergic-response in cultured rat heart cells. Mol Cell Biochem 102, 49–60 (1991). https://doi.org/10.1007/BF00232157

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  • DOI: https://doi.org/10.1007/BF00232157

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