Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-2-23
pubmed:abstractText
The mechanism by which thromboxane A2 (TXA2) causes its detrimental actions on the myocardium during ischemia and reperfusion injury is unknown. The present study was designed to investigate the influence of U46619, a stable TXA2 analog, on intracellular Ca transients in electrically stimulated single neonatal rat ventricular myocytes by using spectrofluorometric analysis of fura-2-Ca binding. Administration of U46619 increased basal and peak Ca concentrations as well as width of electrically induced Ca transients in a concentration-dependent manner (0.1-1 microM) during a 1-hr exposure. Exposure to 10 microM U46619 caused irregular Ca transients and a marked increase in cytosolic-free Ca concentration. The effects of U46619 were antagonized by the TXA2 receptor antagonist SK&F95585 (2 microM), dibutyryl cyclic AMP (1 mM), verapamil (1 microM) and ryanodine (1 microM). U46619 did not affect the increase in cytosolic Ca induced by KCl (90 mM) depolarization. Caffeine (10 mM)-induced Ca release from the sarcoplasmic reticulum was enhanced markedly in U46619-treated cells. Significant lactate dehydrogenase leakage from the myocytes did not occur at 1 to 10 microM U46619. These results indicate that the increase in Ca transients by U46619 is a receptor-mediated process leading to a Ca accumulation in the sarcoplasmic reticulum which is likely to be responsible for an enhanced cytosolic Ca during excitation-contraction coupling. Thus, the identification of U46619-induced alterations of Ca dynamics appears to provide, at the cellular level, a direct role for TXA2 during myocardial ischemia and reperfusion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
336-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Alterations by a thromboxane A2 analog (U46619) of calcium dynamics in isolated rat cardiomyocytes.
pubmed:affiliation
Institute of Industrial Toxicology, Martin Luther University Halle, Federal Republic of Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't