| Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine-induced Ca2+ release from sarcoplasmic reticulum and contractile protein function in 'chemically-skinned' rabbit ventricular trabeculae. | |
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MedLine Citation:
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PMID: 9623719 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Doxorubicin is an anthracycline antibiotic that is used widely as a chemotherapeutic agent. However, the usefulness of this agent is limited due to its cardiotoxic effects. The mechanisms associated with this cardiotoxicity remain essentially unknown, despite numerous studies describing a range of structural and functional abnormalities. The purpose of the present study was to determine the in vivo and in vitro effects of doxorubicin exposure on sarcoplasmic reticulum (SR) Ca2+-content and contractile protein function. The Ca2+-content of SR is shown to have a biphasic response to in vivo and in vitro doxorubicin exposure that is time- and dose-dependent. In vitro doxorubicin exposure initially reduces the SR Ca2+-content, but the predominant action to block the SR Ca2+-release channel increases SR Ca2+-content within 60 min. Similar results are observed with in vivo doxorubicin exposure: it leads to Ca2+-overload. These data are consistent with the view that doxorubicin acts in a similar manner to ryanodine and results in cardiomyopathy due to Ca2+-overload. |
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Authors:
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S Takahashi; M A Denvir; L Harder; D J Miller; S M Cobbe; M Kawakami; N G MacFarlane; E Okabe |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Japanese journal of pharmacology Volume: 76 ISSN: 0021-5198 ISO Abbreviation: Jpn. J. Pharmacol. Publication Date: 1998 Apr |
Date Detail:
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Created Date: 1998-08-05 Completed Date: 1998-08-05 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2983305R Medline TA: Jpn J Pharmacol Country: JAPAN |
Other Details:
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Languages: eng Pagination: 405-13 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and ESR Laboratory, Kanagawa Dental College, Yokosuka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / pharmacology* Caffeine / pharmacology* Calcium / metabolism* Doxorubicin / pharmacology* Heart Ventricles / drug effects*, metabolism Hemodynamics / drug effects Male Myocardial Contraction / drug effects* Rabbits Sarcoplasmic Reticulum / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin; 58-08-2/Caffeine; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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