The action and metabolism of peptide leukotrienes in the isolated bullfrog lung.

Leukotrienes (LTs) have been shown to cause contraction of mammalian airway smooth muscle. In this study, LTC4, LTD4, and LTE4 were tested on isolated strips of bullfrog lung. LTC4, LTD4, and LTE4 (10(-7) to 3 x 10(-10) M) stimulated lung contraction. LTC4 was the most potent, with LTD4 and LTE4 being of equal but lower potency. The cyclooxygenase inhibitors, indomethacin and ibuprofen, had no effect on the strength of leukotriene-induced contraction. In addition, the effects of three mammalian LTD4 receptor antagonists, L-649,923, L-648,051, and LY171883 were tested. All three antagonists failed to block LTC4-simulated contraction, but were effective blockers of LTD4. LTE4-stimulated contractions were significantly blunted by all three antagonists, but the extent of blockade was less than for LTD4. Significant bioconversion of [3H]LTC4 to LTD4 and LTE4 occurred in minced lung preparations but not in lung strips. Peptide leukotrienes caused contraction in amphibian lung, though the order of potency differs from mammals. Like mammals, frogs appear to have two classes of leukotriene receptors, one for LTC4 and one for LTD4-LTE4. These results support the hypothesis that leukotriene receptors have been highly conserved through evolution, despite the fact that the nature of tissue responsiveness to leukotrienes has changed over evolutionary time.