Linked Life Data

10884509

Source:http://linkedlifedata.com/resource/pubmed/id/10884509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2000-9-22
pubmed:abstractText
Phospholipase A(2) plays a crucial role in the release of arachidonic acid (AA) from membrane phospholipids and in myocardial injury during ischemia and reperfusion. Mepacrine, a phospholipase A(2) inhibitor, has been shown to protect the heart from ischemic injury. In order to examine the mechanism of this protection, we investigated the effects of mepacrine on the L-type Ca(2+) current (I(Ca,L)) in rat single ventricular myocytes. Extracellular application of mepacrine significantly inhibited I(Ca,L) in a tonic- and use-dependent manner. The inhibition was also concentration-dependent with an IC(50) of 5.2 microM. Neither the activation nor the steady-state inactivation of I(Ca,L) was altered by mepacrine. The mepacrine-induced inhibition of I(Ca,L) was reversible after washout of the inhibitor. Addition of 1 microM AA partially reversed the mepacrine-induced inhibition of I(Ca,L). Intracellular dialysis, with 2 mM cAMP, significantly increased I(Ca, L), but did not prevent the mepacrine-induced inhibition of I(Ca,L). In addition, extracellular application of isoproterenol or membrane permeable db-cAMP did not reverse the mepacrine-induced inhibition of I(Ca,L). Biochemical measurement revealed that incubation of ventricular myocytes with mepacrine significantly reduced intracellular cAMP levels. The mepacrine-induced reduction of cAMP production was abolished by addition of AA. Our results demonstrate that mepacrine strongly inhibits cardiac I(Ca,L). While mepacrine is a phospholipase A(2) inhibitor and reduces cAMP production, its inhibitory effect on I(Ca,L) mainly results from a direct block of the channel. Therefore, we speculate that the protective effect of mepacrine during myocardial ischemia and reperfusion mostly relates to its blockade of Ca(2+) channels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
399
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
107-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Mechanism of suppression of cardiac L-type Ca(2+) currents by the phospholipase A(2) inhibitor mepacrine.
pubmed:affiliation
The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, 330 Brookline Avenue, Boston MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't