Inotropic, chronotropic, and radioligand binding characteristics of leukotriene B4 in cardiac myocyte, papillary muscle, and membrane preparations.
Cardioprotective effects of dietary fish oil consumption have been attributed to the substitution of eicosapentaenoic acid (EPA) for arachidonic acid (AA) in cellular membranes. This substitution blocks the formation of leukotriene B(4) (LTB(4)) which is elaborated locally in the area of ischemic myocardium. We studied the in vitro inotropic, chronotropic, and radioligand binding characteristics of LTB(4) to gain potentially important insights into the mechanisms involved in the cardioprotective effect of EPA. LTB(4) was a concentration-dependent and reversible negative inotrope in isolated papillary muscle preparations. LTB(4) significantly blocked the positive inotropic effect of Bay K 8644 (BK) (calcium channel regulator) on papillary muscles and the positive chronotropic effect of BK on spontaneously beating neonatal cardiac myocytes. LTB(4) had no direct effect on [(3)H]PN200-110 binding to cardiac sarcolemmal L-type calcium channels or [3H]ryanodine binding to cardiac SR calcium release channels. These studies support a potentially important indirect effect of LTB(4) on myocardial E-C coupling.
Oddis
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Department of Pathology, University of Pittsburgh Medical Center, PA 15213, USA.
Mayer
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Finkel
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D006339:Heart Rate / Q000187:drug effects; D017275:Isradipine / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism* / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011485:Protein Binding; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D002316:Cardiotonic Agents; D012433:Ryanodine; D007975:Leukotriene B4; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D017275:Isradipine