Snyder D W, Krell R D
J Pharmacol Exp Ther. 1984 Dec;231(3):616-22.
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.
在存在和不存在白三烯代谢酶抑制剂的情况下，评估了白三烯（LT）拮抗剂FPL55712对肽类白三烯收缩活性的影响。L-半胱氨酸是一种氨肽酶抑制剂，可阻止LTD4和LTC4形成LTE4。L-丝氨酸硼酸是γ-谷氨酰转肽酶的抑制剂，可阻止LTC4转化为LTD4。L-半胱氨酸（3mM）增强了LTC4和LTD4的收缩活性。L-丝氨酸硼酸（45mM）选择性地增加了LTC4的收缩活性。在不存在酶抑制剂的情况下，FPL55712（10μM）拮抗LTC4、LTD4和LTE4的收缩活性。在存在L-丝氨酸硼酸的情况下，FPL55712（10 - 30μM）未能拮抗LTC4的收缩活性，但确实拮抗了LTD4和LTE4。然而，L-丝氨酸硼酸使FPL55712对LTD4的解离常数（KB）增加，而对LTE4的KB未改变。在存在L-半胱氨酸的情况下，FPL55712拮抗肽类白三烯的收缩活性。然而，在存在L-半胱氨酸的情况下，FPL55712在拮抗LTD4和LTE4方面比拮抗LTC4更有效（P小于0.05）。数据表明，当L-丝氨酸硼酸阻断LTC4向LTD4以及随后向LTE4的转化时，FPL55712在拮抗LTC4的作用方面无效。这表明LTC4在豚鼠气管中占据一个独特的LT受体，该受体对FPL55712的作用不敏感。
