Comparison of the stereoselective effects of a thiadiazinone derivative on contractile parameters and protein phosphorylation in the mammalian ventricle.
In papillary muscles from reserpinized guinea pigs, EMD 57033, the most potent Ca(2+)-sensitizer known, effectively increased force of contraction (FOC) and concomitantly increased duration of contraction. In isolated 32P-labeled guinea pig ventricular cardiomyocytes, EMD 57033 increased the phosphorylation state of phospholamban as well as the inhibitory subunit of troponin, which are usually linked to reductions in contraction time. Therefore, EMD 57033 dissociates phospholamban-phosphorylation and effects on contractile parameters, probably owing to its strong Ca(2+)-sensitizing properties.
Neumann
J
J
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Bokník
P
P
Schmitz
W
W
Scholz
H
H
Zimmermann
N
N
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology*; D013829:Thiadiazines / Q000378:metabolism / Q000494:pharmacology*; D014336:Troponin / Q000378:metabolism; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; D014336:Troponin; D000099211:Phospholamban; C070609:EMD 53998