caa a22 4500 477120121 CHVBK 20180405111634.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/BF00227896 doi (NATIONALLICENCE)springer-10.1007/BF00227896 Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts [Elektronische Daten] [Sabine Bartel, Birgitt Stein, Thomas Eschenhagen, Ulrike Mende, Joachim Neumann, Wilhelm Schmitz, Ernst-Georg Krause, Peter Karczewski, Hasso Scholz] Disturbances in the cAMP production during β-adrenergic stimulation and alterations of Ca 2+ transport controlling proteins and their regulation in the sarcoplasmic reticulum might be involved in the pathogenesis of the failing human heart. Thus, we investigated the cAMP-mediated phosphorylation of phospholamban, troponin I and C-protein in electrically driven, intact isolated trabeculae carneae from nonfailing and failing (NYHA IV) human hearts in parallel to contractile properties on the same tissue samples. The increase in force of contraction induced by isoproterenol (0.2 μM) or pimobendan (100 μM), a phosphodiesterase inhibitor, was diminished in the failing human hearts compared to nonfailing hearts by 49% and 36%, respectively. Concomitantly the isoproterenol-induced phosphorylation (pmol P/mg homogenate protein) of phospholamban, troponin I and C-protein was reduced from 13.0 ± 2.4 (n = 4), 30.5 ± 1.5 (n = 5) and 11.0 ± 1.3 (n = 5) in the nonfailing heart to 5.2 ±0.6 (n = 13), 14.6 ± 2.2 (n = 16) and 7.1 ± 1.0 (n = 6) in the failing human heart, respectively. Pimobendan changed the phosphorylation state of these proteins similar to isoproterenol. The fact that combined addition of both agents or dibuturyl CAMP (1 mM) alone restored the phosphorylation capacity as observed in the control groups indicates that i) a reduced cAMP generation is related to the reduced phosphorylation of regulatory phosphoproteins located in the sarcoplasmic reticulum and contractile apparatus e.g. phospholamban, troponin I and C-protein, that ii) there is a relationship between protein phosphorylation state and contractile activity and that iii) no changes in the respective content of phosphoproteins are involved in the limitation of cAMP-mediated inotopic activity in the failing human heart. (Mol Cell Biochem 157: 171-179, 1996) Kluwer Academic Publishers, 1996 human heart nationallicence force of contraction nationallicence protein phosphorylation nationallicence phospholamban nationallicence Bartel Sabine Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut Stein Birgitt Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut Eschenhagen Thomas Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut Mende Ulrike Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut Neumann Joachim Institut für Pharmakologie und Toxikologie der Universität Münster, Germany aut Schmitz Wilhelm Institut für Pharmakologie und Toxikologie der Universität Münster, Germany aut Krause Ernst-Georg Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut Karczewski Peter Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut Scholz Hasso Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 171-179 0300-8177 157:1-2<171 1996 157 11010 https://doi.org/10.1007/BF00227896 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00227896 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bartel Sabine Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut NATIONALLICENCE 700 1- Stein Birgitt Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut NATIONALLICENCE 700 1- Eschenhagen Thomas Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut NATIONALLICENCE 700 1- Mende Ulrike Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut NATIONALLICENCE 700 1- Neumann Joachim Institut für Pharmakologie und Toxikologie der Universität Münster, Germany aut NATIONALLICENCE 700 1- Schmitz Wilhelm Institut für Pharmakologie und Toxikologie der Universität Münster, Germany aut NATIONALLICENCE 700 1- Krause Ernst-Georg Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut NATIONALLICENCE 700 1- Karczewski Peter Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany aut NATIONALLICENCE 700 1- Scholz Hasso Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 171-179 0300-8177 157:1-2<171 1996 157 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer