Bioconversion of leukotriene C4 by the 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. LTC4 was the most potent of the leukotrienes tested in eliciting positive inotropic effects. LTD4 and LTE4 were equally effective but about one order of magnitude less potent than LTC4. None of the LTs showed any chronotropic effects in this preparation. LTC4 was significantly more potent in the presence of L-serine borate, an inhibitor of gamma-glutamyl transpeptidase, than in its absence, raising the possibility of significant bioconversion of LTC4 by the bullfrog heart. 3H-LTC4 metabolism experiments were carried out using whole perfused hearts or minced bullfrog heart tissue. During the six minute course of collection, the isolated perfused heart converted significant amounts of LTC4 to LTD4 and to a lesser degree LTE4. This conversion was attenuated in the presence of L-serine borate. Both minced atrial and ventricular tissue converted 3H-LTC4 to radioactive metabolites which co-migrated with authentic LTD4 and LTE4 standards. In both tissues, the major product was LTD4, with smaller amounts of LTE4 produced. The atrium converted significantly more LTC4 to its metabolites than did the ventricle. The metabolism of LTC4 to LTD4 by both tissues was virtually abolished in the presence of serine borate. It is interesting that LTC4 metabolism pattern and rate is comparable in mammals and frogs in spite of the fact that the inotropic effects of leukotrienes are opposite in the two taxa and, in frogs, metabolism results in a less potent agent.