The production of leukotrienes and their orignal cellular species were investigated using isolated bufferperfused rat hearts. By administration of A23187, a calcium ionophore, the production of leukotriene B
4 and C
4 increased significantly, reached the maximum level at 10 min, and then gradually decreased. The total amounts of leukotrienes produced during the 30 min were 39.1±8.0and 143.5 ± 18.4ng/g heart for leukotriene B
4 and C
4, respectively. The A23187-induced production of leukotrienes was dependent on the extracellular calcium concentration and was significantly suppressed by AA861, a 5-lipoxygenase inhibitor, which indicates that the calcium influx triggers the prodution of leukotrienes via the 5-lipoxygenase pathway. On the other hand, myocardial calcium-overload induced by caffeine administration and calcium paradox did not increase the leukotriene production, which suggests that myocardial cells are not involved in the leukotriene production. The presence of mast cells in the perivascular area of the heart was histologically observed. Furthermore, cromolyn, a suppressive agent of mast cells, significantly suppressed the cardiac leukotriene production. These findings suggest that mast cells and the origin of leukotrienes produced by isolated heart.
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