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

Abstract Cumulative dose-response curyes to leukotriene C 4 (LTC 4 ) and leukotriene D 4 (LTD) 4 were obtained on indomethacin (5 μM) treated isolated guinea pig tracheal spiral strips. LTC 4 curves, in the presence of either glutathione (GSH; 10 mM) or L-serine borate (SB; 45 mM), were not antagonized by FPL-55712 (3 μM), a selective LTD 4 receptor antagonist. LTC 4 curves on trachea treated with a lower concentration of GSH (1 mM), and LTD 4 curves were competitively antagonized by FPL-55712. LTC, 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 nordihydro-guiaretic acid (30 μM), an inhibitor of 5-lipoxygenase. GSH (10 μM) and SB (45 mM) are effective inhibitors of conversion of LTC 4 into functionally important levels of LTD 4 by the guinea pig trachea. In addition, GSH appeares to enhance LTC 4 responsiveness by increasing synthesis of a contractile 5-lipoxygenase product(s), possibly LTC 4 . From the data it is suggested that for inhibition of LTC 4 metabolism, SB may be more usefull when examining responses to exogenously applied LTC 4 , while GSH (10 mM) may be useful when examining responses to endogenously generated LTC 4 .