| Abstract: | We have studied the effects of a lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on antagonim of leukotriene (LT) C4-induced contractions of isolated guinea-pig trachea and the results were compared to that of a cycloocygenase inhibitor indomethacin, NDGA (30 μM) as well as idomethacin (5 μM) inhibited LTC4-iduced contraction. But in the presence of indomethacin NDGA was ineffective to inhibit the LTC4 response, whereas two other lipoxygenase inhibitors, phenidone (3–30 μM) and 5,8,11,14-eicostatetraynoic acid (ETYA, 10 μM), markedly inhibited it. The antagonist action of an LTD4 receptor antagonist FPL55712 against LTC4-induced contractions was significantly reduced by NDGA (10–30 μM), but indomethacin had no effect on it. NDGA possessed the same inhibitory effect n the LTC4 antagonism in the presence of indomethacin, but 0.3 μM phenidone and 1 μM ETYA which did not inhibit the LTC4 response had no effect on it. NDGA also inhibited the relaxant response of isoproterenol on the contraction elicited by 30 nM LTC4, but did not affect those of forskolin and aminophylline. The relaxant response of isoproterenol on the LCT4 response was not inhibited by indomethacin, 0.3 μM phenidone and 1 μM ETYA. In the presence of a γ-glutamyltranspeptidase inhibitor, L-serine borate (SB, 45 mM), NDGA had no effect on the LTC4 antagonism and the relaxant response of isoproterenol. In contrast, NDGA significantly inhibited the relaxant response of isoproterenol on 30 μM histamine- and 30 μM acetylcholine-induced contractions, but it did not affect the histamine antagonism by a histamine H1-blocker pyrilamine. These results suggest that some putative nonprostanoids are involved in LTC4-induced contractions of guinea-pig trachea and which regulate the effects of LTD4 antagonism and β-adrenoceptor activation. |
