Reduction of myocardial cross-bridge turnover rate in presence of EMD 53998, a novel Ca(2+)-sensitizing agent.
We have studied the effect of EMD 53998 (5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl)-6-me thyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one) on cross-bridge turnover rate at varying Ca2+ concentrations. Cross-bridge cycling rate was estimated both by adenosine triphosphatase measurements and determination of mechanical characteristics of constantly activated fibres, which is assumed to reflect cross-bridge kinetics. The results indicate that the turnover rate of myocardial cross-bridges was reduced in the presence of EMD 53998 at low Ca2+ concentrations (pCa greater than or equal to 6.25), but not at higher Ca2+ concentrations (pCa less than or equal to 5.85).
Leijendekker
W J
WJ
Department Research CVS, Ciba-Geigy Limited, Basle, Switzerland.
Herzig
J W
JW
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000187:drug effects / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D013552:Swine; D013829:Thiadiazines / Q000494:pharmacology*; D016276:Ventricular Function
D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D009218:Myosins; D002118:Calcium