Abstract

The effect of the leukotriene (LT) antagonist, FPL55712, on the contractile activity of peptide leukotrienes was evaluated in the presence and absence of enzyme inhibitors of leukotriene metabolism. L-Cysteine, an inhibitor of aminopeptidase, prevents the formation of LTE4 from LTD4 and LTC4. L-Serine borate, an inhibitor of gamma-glutamyl transpeptidase prevents the conversion of LTC4 to LTD4. L-Cysteine (3mM) enhanced the contractile activity of LTC4 and LTD4. L-Serine borate (45 mM) increased selectively the contractile activity of LTC4. FPL55712 (10 microM) antagonized the contractile activity of LTC4, LTD4 and LTE4 in the absence of enzyme inhibitors. In the presence of L-serine borate, FPL55712 (10-30 microM) failed to antagonize the contractile activity of LTC4 but did antagonize LTD4 and LTE4. However, the dissociation constant (KB) for FPL55712 against LTD4 was increased by L-serine borate whereas the KB against LTE4 was not altered. In the presence of L-cysteine, FPL55712 antagonized the contractile activity of the peptide LTs. However, FPL55712 was more effective (P less than .05) in antagonizing LTD4 and LTE4 than LTC4 in the presence of L-cysteine. The data suggest that when the conversion of LTC4 to LTD4 and subsequently to LTE4 is blocked by L-serine borate FPL55712 is ineffective in antagonizing the actions of LTC4. This would indicate that LTC4 occupies a distinct LT receptor in guinea-pig trachea which is insensitive to the actions of FPL55712.