CHARACTERIZATION OF SULFIDOPEPTIDE LEUKOTRIENE RESPONSES IN SHEEP TRACHEAL SMOOTH-MUSCLE INVITRO

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100-mu-M. Indomethacin (5-mu-M) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of gamma-glutamyl transpeptidase, shifted the dose - response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose - response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1-mu-M), an LT antagonist, shifted the dose - response curves of LTC4 and LTD4 to the right with pK(B) values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1-mu-M) shifted the dose-response curves of LTC4 and LTD4 to the right with pK(B) values of 6.87 and 7.31, respectively. YM-17690 (10-mu-M) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.