Leukotriene C4action and metabolism in the isolated perfused bullfrog heart

摘要

The effects of leukotrienes (LTs) have been widely studied in the isolated perfused mammalian heart; however, little is known about the effect or metabolism of LTs in the isolated bullfrog heart. Isolated perfused bullfrog hearts were administered randomized doses of LTC4, LTD4, or LTE4. The cardiac parameters of heart rate, developed tension, and its first derivative (dT/dt) were recorded. LTC4was the most potent of the leukotrienes tested in eliciting positive inotropic effects. LTD4and LTE4were equally effective but about one order of magnitude less potent than LTC4. None of the LTs showed any chronotropic effects in this preparation. A series of 3HLTC4metabolism experiments were carried out using whole perfused hearts and minced bullfrog heart tissue. Isolated perfused bullfrog hearts administered 3HLTC4converted significant amounts to 3HLTD4, and to a lesser degree, 3HLTE4, during the 6-min course of collection. Both minced atrial and ventricular tissue converted 3HLTC4to radioactive metabolites that co-migrated with authentic LTD4and LTE4standards. In both tissues, the major product was 3HLTD4, with smaller amounts of 3HLTE4produced. The atrium converted significantly more 3HLTC4to its metabolites than did the ventricle. The metabolism of 3HLTC4to 3HLTD4by both tissues was virtually abolished in the presence of serine borate. Cysteine had no effect on 3HLTE4production. The data in this study demonstrate that leukotrienes have the opposite inotropic effect on the heart when compared with mammals. Also in contrast to mammals, frogs metabolize LTC4to a less potent compound and may use the LTC4to LTD4conversion as a mechanism of LTC4inactivation.