Mechanisms of the contractile effects of 2,3-butanedione-monoxime in the mammalian heart. 1996

N Zimmermann, and P Boknik, and E Gams, and S Gsell, and L R Jones, and R Maas, and J Neumann, and H Scholz
Klinik für Thorax- und Kardiovaskuläre Chirurgie, Heinrich Heine-Universität, Düsseldorf, Germany.

We studied the mechanisms of action of a negative inotropic compound, 2,3-butanedione-monoxime (BDM), which has been suggested to be a cardioprotective agent. In guinea-pig papillary muscles the negative inotropic effect of BDM start at 100 mumol/l amounting to 18.32 +/- 2.09% of predrug value at 10 mmol/l without any effects on time parameters (n = 12, each). 30 mmol/l BDM totally abolished force of contraction; this effect was reversible after washout. In the presence of the phosphatase-inhibitor cantharidin (30 mumol/l) the concentration response curve on force of contraction was shifted to higher concentrations of BDM. 100 mmol/l BDM decreased the phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes to 76.5 +/- 4.7% and 49.7 +/- 4.2%, respectively (n = 7). Furthermore, BDM enhanced the activity of phosphorylase phosphatases in guinea-pig ventricular homogenates amounting to a stimulation to 203.5 +/- 10.4% at 100 mmol/l whereas type 1 phosphorylase phosphatase activity increased only by 24.5% (n = 5). PLB phosphatase activity was enhanced to 155.9 +/- 11.7% by 100 mmol/l BDM (n = 5). It is concluded that the effects of BDM on contractile parameters are accompanied by decreased phosphorylation of the cardiac regulatory proteins TnI and PLB which could in part be due to activation of type 1 or 2A phosphatase activity. Hence, it is suggested that BDM affects the phosphorylation state of TnI and PLB not directly, but via activation of their phosphatases.

UI MeSH Term Description Entries
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010749 Phosphoprotein Phosphatases A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D010765 Phosphorylase Phosphatase An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 3.1.3.17. Glycogen Phosphorylase Phosphatase,Phosphatase, Glycogen Phosphorylase,Phosphatase, Phosphorylase,Phosphorylase Phosphatase, Glycogen
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002135 Calcium-Binding Proteins Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS. Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D003931 Diacetyl Carrier of aroma of butter, vinegar, coffee, and other foods. 2,3-Butanedione,Biacetyl,Diketobutane,Dimethyldiketone,Dimethylglyoxal,2,3 Butanedione
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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