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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-9-18
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pubmed:abstractText |
In electrically driven guinea pig left atria, plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone; 0.5-10 microM) produced a marked positive inotropic effect that was about 65% that caused by isoprenaline in the same experimental conditions. The effect was mainly not dependent on catecholamine release from adrenergic stores. An EC50 of 3 microM was calculated from the concentration-response curves. The increase in force of contraction was followed by a nonreversible contracture. Plumbagin was reduced by cardiac mitochondrial and soluble reductases with consequent generation of large amounts of superoxide anion. The assay of reduced glutathione/oxidized glutathione content in atria, treated with 10 microM plumbagin and frozen at the appearance of increase in diastolic tension, showed a significant decrease in reduced glutathione (-52% with respect to control atria) and a 5-fold increase in oxidized glutathione levels. Moreover, in the same experimental conditions a significant decrease in adenosine triphosphate (-55% with respect to the controls) and in adenylate energy charge (from 0.92-0.64) was observed. Of the enzymes and transport systems involved in the control of the cardiac contractility, the sarcoplasmic reticulum Ca2+ pump seemed to be a specific target for plumbagin. After 30 min of incubation with cardiac sarcoplasmic reticulum membrane vesicles, plumbagin inhibited Ca2+ uptake by the pump in a concentration-dependent manner (IC50 = 3 microM). On the basis of these results, the increase in diastolic tension caused by plumbagin appears to be related to intracellular Ca2+ accumulation, due both to the low availability of adenosine triphosphate for ionic pumps and direct inhibition of Ca2+ reuptake in sarcoplasmic reticulum.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
763-70
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8768729-Animals,
pubmed-meshheading:8768729-Cardiotonic Agents,
pubmed-meshheading:8768729-Dose-Response Relationship, Drug,
pubmed-meshheading:8768729-Guinea Pigs,
pubmed-meshheading:8768729-Heart Atria,
pubmed-meshheading:8768729-Isoproterenol,
pubmed-meshheading:8768729-Naphthoquinones
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pubmed:year |
1996
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pubmed:articleTitle |
Mechanisms of plumbagin action on guinea pig isolated atria.
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pubmed:affiliation |
Department of Pharmacology, University of Padova, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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