Pharmacological comparison of L-serine borate and glutathione as inhibitors of metabolism of LTC4 to LTD4 by the isolated guinea pig trachea.

Cumulative dose-response curves to leukotriene C4 (LTC4) and leukotriene D4 (LTD)4 were obtained on indomethacin (5 microM) treated isolated guinea pig tracheal spiral strips. LTC4 curves, in the presence of either glutathione (GSH; 10 mM) or L-serine borate (SB; 45 mM), were not antagonized by FPL-55712 (3 microM), a selective LTD4 receptor antagonist. LTC4 curves on trachea treated with a lower concentration of GSH (1 mM), and LTD4 curves were competitively antagonized by FPL-55712. LTC4 curves on GSH (10 mM) treated trachea were 2 fold to the left of those on SB treated tissues. This effect of GSH was blocked by pretreatment with nordihydroguiaretic acid (30 microM), an inhibitor of 5-lipoxygenase. GSH (10 mM) and SB (45 mM) are effective inhibitors of conversion of LTC4 into functionally important levels of LTD4 by the guinea pig trachea. In addition, GSH appears to enhance LTC4 responsiveness by increasing synthesis of a contractile 5-lipoxygenase product(s), possibly LTC4. From the data it is suggested that for inhibition of LTC4 metabolism, SB may be more useful when examining responses to exogenously applied LTC4, while GSH (10 mM) may be more useful when examining responses to endogenously generated LTC4.