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On the mechanism of positive inotropic effects of alpha-adrenoceptor agonists

  • Cellular And Subcellular Mechanisms, Energy Turnover
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Summary

The positive inotropic effect of the alpha1-adrenoceptor agonist phenylephrine is accompanied by an increase in the presumed second messengers inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4). Both 1,4,5-IP3 and 1,3,4,5-IP4 sensitize myocardial contractile proteins in chemically skinned fibers. In addition to the Ca++ releasing effect of 1,4,5-IP3 from the sarcoplasmic reticulum the Ca++-sensitizing effect of the inositol phosphates may play a role in alpha1-adrenergic positive inotropism. In isolated heart muscle preparations from patients with endstage heart failure (due to dilated cardiomyopathy) beta-adrenergic as well as alpha1-adrenergic effects are reduced compared to preparations from healthy hearts. The reduced beta-adrenergic effects can in part be explained by an increased content of signal transducing G1-proteins. It is tempting to investigate whether other G proteins are also altered in severe congestive heart failure.

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Authors and Affiliations

  1. Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Martinistraße 52, D-2000, Hamburg 20, FRG

    W. Schmitz, C. Kohl, J. Neumann, H. Scholz & J. Scholz

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  1. W. Schmitz
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  2. C. Kohl
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  3. J. Neumann
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  4. H. Scholz
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  5. J. Scholz
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Schmitz, W., Kohl, C., Neumann, J. et al. On the mechanism of positive inotropic effects of alpha-adrenoceptor agonists. Basic Res Cardiol 84, 23–33 (1989). https://doi.org/10.1007/BF02650344

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