Calcium-ionophore stimulated release of leukotriene C4-like immunoreactive material from cardiac tissue.
Administration of leukotrienes to cardiac tissue produces contractile depression and coronary artery constriction [5,8], thus making it possible that these substances mediate cardiac dysfunction under pathologic conditions. Up to now no studies have been performed to determine whether cardiac tissue has the inherent ability to produce leukotrienes. The present study was therefore carried out to ascertain whether isolated hearts perfused with saline buffer devoid of any blood constituents can produce leukotrienes under a variety of pharmacologic and pathologic situations. No leukotriene (LT) C4 was detected under control conditions or from hearts subjected to global ischemia and reperfusion or hypoxia and reoxygenation. A23187, a Ca2+ ionophore markedly stimulated LTC4 release. This effect was prevented by nordihydroguaiaretic acid, a selective lipoxygenase inhibitor. The addition of arachidonate as substrate had no effect on LTC4 release. In an attempt to divert arachidonate to LTC4 production, indomethacin, a cyclo-oxygenase inhibitor was added before arachidonate. No LTC4-like immunoreactivity was found in these experiments. These studies suggest that a lipoxygenase pathway for leukotriene production is present either in the coronary vasculature or myocardium. It was stimulated only by Ca2+ ionophore, probably indicating a requirement for high amounts of intracellular Ca2+.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D000001:Calcimycin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis / Q000378:metabolism*
D013189:SRS-A; D000001:Calcimycin; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase