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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1991-10-9
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pubmed:abstractText |
The mechanism of doxorubicin-induced Ca2+ release from skeletal and cardiac muscle sarcoplasmic reticulum (SR) was studied by examining the effects of azumolene (a water soluble dantrolene analog) on doxorubicin-mediated Ca2+ release and ryanodine binding. Doxorubicin induced a rapid Ca2+ release from both skeletal and cardiac SR in a similar concentration range (EC50 = 5-10 microM). Maximal doxorubicin-induced Ca2+ release was seen at 2 and 0.2 microM Ca2+ for skeletal and cardiac SR, respectively. Addition of 400 microM azumolene caused approx. 30% inhibition of doxorubicin-induced Ca2+ release from both skeletal and cardiac SR; skeletal SR had significantly higher sensitivity to azumolene than cardiac SR. In the presence of Ca2+, doxorubicin increased [3H]ryanodine binding to both skeletal and cardiac SR; whereas in the absence of Ca2+, doxorubicin led to significant ryanodine binding to skeletal SR, but not to cardiac SR. In both types of SR, doxorubicin-activated, but not Ca2+ activated ryanodine binding was inhibited by azumolene. Azumolene sensitivity for inhibition of doxorubicin-activated ryanodine binding was much higher in skeletal SR than cardiac SR, consistent with the results for effects of azumolene on Ca2+ release. Our results are consistent with the possibility that azumolene inhibits doxorubicin binding by direct competition for the drug receptor(s).
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cholinergic,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release...,
http://linkedlifedata.com/resource/pubmed/chemical/azumolene
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
1094
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27-34
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1883852-Animals,
pubmed-meshheading:1883852-Binding, Competitive,
pubmed-meshheading:1883852-Calcium,
pubmed-meshheading:1883852-Doxorubicin,
pubmed-meshheading:1883852-Imidazoles,
pubmed-meshheading:1883852-Muscles,
pubmed-meshheading:1883852-Myocardium,
pubmed-meshheading:1883852-Oxazoles,
pubmed-meshheading:1883852-Rabbits,
pubmed-meshheading:1883852-Receptors, Cholinergic,
pubmed-meshheading:1883852-Ryanodine,
pubmed-meshheading:1883852-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:1883852-Sarcoplasmic Reticulum
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pubmed:year |
1991
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pubmed:articleTitle |
Effects of azumolene on doxorubicin-induced Ca2+ release from skeletal and cardiac muscle sarcoplasmic reticulum.
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pubmed:affiliation |
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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