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Research ArticleArticle

Inotropic Effects of Diadenosine Tetraphosphate (AP4A) in Human and Animal Cardiac Preparations

U. Vahlensieck, P. Bokník, I. Gombosová, S. Huke, J. Knapp, B. Linck, H. Lüβ, F. U. Müller, J. Neumann, M. C. Deng, H. H. Scheld, H. Jankowski, H. Schlüter, W. Zidek, N. Zimmermann and W. Schmitz
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 805-813;
U. Vahlensieck
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P. Bokník
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I. Gombosová
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S. Huke
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J. Knapp
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B. Linck
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H. Lüβ
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F. U. Müller
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J. Neumann
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M. C. Deng
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H. H. Scheld
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H. Jankowski
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H. Schlüter
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W. Zidek
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N. Zimmermann
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Abstract

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1–100 μM) reduced FOC maximally by 36.5 ± 4.3%. In guinea pig papillary muscles, AP4A (100 μM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 ± 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 μM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 μM) alone increased FOC to 158.3 ± 12.4% and 167.5 ± 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 μM) reduced FOC by 27.2 ± 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after betaadrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Footnotes

  • Send reprint requests to: Dr. med. Ute Vahlensieck, Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Domagkstr. 12, D-48129 Münster, Germany.

  • ↵1 Current address: Klinik und Poliklinik für Thorax-, Herz-, Gefäβchirurgie, Westfälische Wilhelms-Universität Münster, Germany.

  • ↵2 Current address: Medizinische Klinik I, Marienhospital Herne, Ruhr-Universität Bochum, Germany.

  • ↵3 Current address: Klinik für Thorax- und Kardiovaskuläre Chirurgie, Heinrich Heine-Universität Düsseldorf, Germany.

  • Abbreviations:
    APnAs
    diadenosine polyphosphates
    AP4A
    diadenosine tetraphosphate
    DPCPX
    1,3-dipropyl-cyclopentylxanthine
    R-PIA
    (−)-N6-phenylisopropyladenosine
    FOC
    force of contraction
    ICaL
    L-type calcium current
    [Ca]i
    intracellular calcium concentration
    • Received March 23, 1998.
    • Accepted August 4, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Inotropic Effects of Diadenosine Tetraphosphate (AP4A) in Human and Animal Cardiac Preparations

U. Vahlensieck, P. Bokník, I. Gombosová, S. Huke, J. Knapp, B. Linck, H. Lüβ, F. U. Müller, J. Neumann, M. C. Deng, H. H. Scheld, H. Jankowski, H. Schlüter, W. Zidek, N. Zimmermann and W. Schmitz
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 805-813;

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Research ArticleArticle

Inotropic Effects of Diadenosine Tetraphosphate (AP4A) in Human and Animal Cardiac Preparations

U. Vahlensieck, P. Bokník, I. Gombosová, S. Huke, J. Knapp, B. Linck, H. Lüβ, F. U. Müller, J. Neumann, M. C. Deng, H. H. Scheld, H. Jankowski, H. Schlüter, W. Zidek, N. Zimmermann and W. Schmitz
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 805-813;
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