Inhibition of calmodulin-dependent and independent cardiac sarcoplasmic reticulum activities by R24571.
R24571 a derivative of the antimycotic miconazole, appears to be 5 to 8 times more potent than trifluoperazine in its ability to inhibit the calmodulin-dependent phosphorylation of cardiac sarcoplasmic reticulum vesicles. The cAMP-dependent protein kinase mediated phosphorylation of cardiac sarcoplasmic reticulum was not affected by R24571. Sarcoplasmic reticulum Ca-dependent ATPase phosphoprotein intermediate formation was inhibited by R24571 concentrations that were 20 to 30 times greater than those required to inhibit calmodulin-dependent phosphorylation. However, both Ca-dependent and independent ATPase activities, as well as calcium uptake, were inhibited by R24571 concentrations that were similar to, or less than, those concentrations required to inhibit calmodulin-dependent sarcoplasmic reticulum phosphorylation. These results indicate the caution that should be exercised in using this new compound in assessing the possible involvement of calmodulin in other membrane processes.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000494:pharmacology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D014268:Trifluoperazine / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D014268:Trifluoperazine; C031938:calmidazolium; D011494:Protein Kinases; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases