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

I. Beta-adrenergic supersensitivity is induced by lactate via a phospholipase A2 and 15-lipoxygenase involving pathway

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Abstract

Incubation of rocker-cultured neonatal rat heart cells with 3 mM L(+)-lactate led to a sharp increase in the sensitivity of cardiomyocytes to the beta-adrenergic agonist isoprenaline, as measured by their chronotropic response. This effect was accompanied by a reduction in the arachidonic acid content of the total phospholipids. The phospholipase A2-activator melittin as well as free arachidonic acid induced this supersensitivity to the same degree. On the other hand, the L(+)-lactate-evoked supersensitivity could be blocked by the phospholipase A2 inhibitors mepacrine and n-bromophenacyl-bromide, suggesting an involvement of phospholipase A2 in the process of beta-adrenergic sensitization. The sensitizing action of arachidonic acid was blocked by the lipoxygenase inhibitors esculetin and nordihydroguaiaretic acid, but not by the cyclooxygenase inhibitor indomethacin. Supersensitivity was likewise evoked by 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), but not by 5-S-HPETE or 5-S-HETE. These findings suggest that the phospholipase A2-15-lipoxygenase pathway plays a role in the induction of beta-adrenergic supersensitivity in the cultured cardiomyocytes and point to a new physiological role of the lipoxygenase product 15-S-HETE.

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Abbreviations

NDGA:

nordihydroguaiaretic acid

HETE:

hydroeicosatetraenoic acid

HPETE:

hydroperoxyeicosatetraenoic acid

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Authors and Affiliations

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

    Gerd Wallukat & Albert Wollenberger

  2. Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

    Gyorgy Nemecz & Tibor Farkas

  3. Institute of Biochemistry, Humboldt-University of Berlin, Berlin, Germany

    Hartmut Kuehn

Authors
  1. Gerd Wallukat
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  2. Gyorgy Nemecz
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  3. Tibor Farkas
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  4. Hartmut Kuehn
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  5. Albert Wollenberger
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Wallukat, G., Nemecz, G., Farkas, T. et al. Modulation of the beta-adrenergic response in cultured rat heart cells. Mol Cell Biochem 102, 35–47 (1991). https://doi.org/10.1007/BF00232156

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  • DOI: https://doi.org/10.1007/BF00232156

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