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Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium

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Abstract

In human ventricular trabeculae carneae 100 µM AP4A (diadenosine tetraphosphate) increased force of contraction to 162.8±15.7% of predrug value (n=9). This positive inotropic effect was accompanied by a prolongation of time parameters: time to peak tension and time of relaxation were prolonged by 7.8±1.3% and 14.9±3.8%, respectively (P<0.05). In the same trabeculae, AP4A increased IP3 (inositol-1,4,5-trisphosphate) content from 9.0±1.3 pmol/mg to 22.9±5.4 pmol/mg protein (n=5–9).

In conclusion, the positive inotropic effect of AP4A in the human myocardium is likely due to an increase of IP3 mediated probably via Gq-coupled P2Y-purinoceptors. Because of the prominent role of Gq in the development of cardiac disease, these findings may lay the ground to further investigate the possible role of AP4A and/or related ligands (e.g. AP2A and AP3A) in heart failure.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Domagkstrasse 12, D-48129 Münster, Germany

    J. Knapp, P. Bokník, B. Linck, F.U. Müller, J. Neumann, U. Vahlensieck & W. Schmitz

  2. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitäts-Krankenhaus Eppendorf, D-20246 Hamburg, Germany

    S. Läer

  3. Ruhr-Universität Bochum, Marienhospital – Innere Medizin, D-44625 Herne, Germany

    H. Schlüter & W. Zidek

Authors
  1. J. Knapp
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  2. P. Bokník
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  3. B. Linck
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  4. S. Läer
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  5. F.U. Müller
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  6. J. Neumann
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  7. U. Vahlensieck
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  8. H. Schlüter
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  9. W. Zidek
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  10. W. Schmitz
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Knapp, J., Bokník, P., Linck, B. et al. Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium. Naunyn-Schmiedeberg's Arch Pharmacol 360, 354–357 (1999). https://doi.org/10.1007/s002109900076

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  • DOI: https://doi.org/10.1007/s002109900076

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