Drug interaction with cardiac and skeletal muscle troponin C.
The effects of certain drugs on the binding of divalent cations to Ca(2+)-specific and Ca/Mg sites on cardiac and skeletal troponin C molecules were investigated by fluorescence and circular dichroism spectroscopy. Nicardipine and two new cardiotonic agents, APP 201-533 and DPI 201-106, interact with the N-terminal domain of troponin C, and either do not affect or, in the case of DPI 201-106, slightly increase the affinity of the Ca(2+)-specific site of troponin C for Ca2+ ion. Compound 48/80 seems to interact with the central alpha-helix of skeletal troponin C and affects the cation-binding properties of both the Ca(2+)-specific and the Ca/Mg sites of the protein. Trifluoperazine and calmidazolium (R24571) interact with the C-terminal domain of troponin C and increase the affinity of the Ca/Mg sites located there. At high concentrations these compounds interact with the N-terminal domain of troponin C and increase the affinity of the Ca(2+)-specific site. According to fluorescence spectroscopy data, R24571 induces conformational changes in troponin C similar to those evoked by troponin I. The experimental data suggest that the drugs studied act in similar ways with troponin C and calmodulin.
Geguchadze
R N
RN
Department of Biochemistry, School of Biology, Moscow State University, USSR.
Krylatov
A V
AV
Gusev
N B
NB
D000495:Allosteric Site / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002417:Cattle; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology; D011817:Rabbits; D014268:Trifluoperazine / Q000494:pharmacology; D014336:Troponin / Q000187:drug effects / Q000378:metabolism*; D019209:Troponin C; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002147:Calmodulin; D002316:Cardiotonic Agents; D007093:Imidazoles; D010879:Piperazines; D011728:Pyridones; D014336:Troponin; D019209:Troponin C; D014268:Trifluoperazine; D003189:p-Methoxy-N-methylphenethylamine; C031938:calmidazolium; C045982:3-amino-6-methyl-5-phenyl-2(1H)-pyridinone; C046261:DPI 201-106; D009529:Nicardipine; D008274:Magnesium; D002118:Calcium