Biphasic positive inotropic actions of doxorubicin in isolated guinea pig hearts: relation to Ca2+ release from the sarcoplasmic reticulum.
Doxorubicin (30 microM) caused a biphasic (early and late phase) positive inotropic effect. A high concentration (200 microM) of this agent caused a stronger early phase, but a weaker late phase. The early phase caused by the high concentration of doxorubicin was significantly reduced by cyclopiazonnic acid or thapsigargin, although it was not altered by ryanodine, verapamil, or nifedipine. The late phase in the presence of the high concentration of doxorubicin was slightly enhanced by cyclopiazonic acid, verapamil or nifedipine, and markedly enhanced by ryanodine. At the end of the 4-hr experimental period in the presence of the high concentration of doxorubicin, the positive inotropic effects of CaCl2 were completely diminished. Verapamil almost completely restored the action of the doxorubicin.
Temma
K
K
Department of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan. temma@vmas.kitasato-u.ac.jp
Chugun
A
A
Hara
Y
Y
Sasaki
T
T
Kondo
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D012433:Ryanodine; D019284:Thapsigargin; D004317:Doxorubicin; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002122:Calcium Chloride; D002118:Calcium; C000543:cyclopiazonic acid