The role of calcium-binding proteins in the mechanism of action of cardioactive substances.
This study, performed on pure muscular regulatory proteins and contracting myocytes in embryonal myocardial cultures, showed a direct interaction of the tropomyosin-troponin complex (TM-TN) with beta-adrenergic and Ca2+-channel-blocking agents. The TM-TN complex incorporates into the myocyte membranes as well as into artificial membranes, inducing changes in the X-ray diffraction picture. This protein complex prevents the inhibitory effect of D-600, propranolol, and other agents on the contraction of myocytes, restores the sensitivity of the cells to catecholamines, and promotes transmembrane transport of Ca2+ . beta-Adrenergic agents decrease the melting point and increase the intramolecular mobility of the TM-TN complex. They activate the Mg2+ ATPase of native but not desensitized actomyosin. In this case, they do not compete with Ca2+ for the same sites. The role of the direct interaction of cardioactive agents with the Ca2+-binding proteins in the membranes and other compartments of the cell is discussed in connection with their mechanism of action on the myocardium.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002642:Chick Embryo; D004837:Epinephrine / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D008274:Magnesium / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology; D014335:Tropomyosin / Q000378:metabolism; D014336:Troponin / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D007473:Ion Channels; D011941:Receptors, Adrenergic; D014335:Tropomyosin; D014336:Troponin; D011433:Propranolol; D013806:Theophylline; D000251:Adenosine Triphosphatases; D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine