Baker S R, Boot J R, Gooderham R, O'Brien A, Thomas K H, Ward M, Woodhouse S
Lilly Research Centre Limited, Eli Lilly & Co., Windlesham, Surrey, England.
Prostaglandins. 1990 Nov;40(5):445-61. doi: 10.1016/0090-6980(90)90108-8.
N-methyl LTC4 (NMLTC4) a synthetic analogue of LTC4, has been shown not to be a substrate for gamma-glutamyl transpeptidase. NMLTC4 produced contractions of the guinea pig ileum and trachea with pD2 values of 7.7 +/- 0.12 (n = 6) and 8.1 +/- 0.1 (n = 6) respectively, compared with values of 9.0 +/- 0.1 (n = 5) and 8.0 +/- 0.2 (n = 6) for LTC4. The concentration-response curve to LTC4 and NMLTC4 on ileum was displaced to the right by FPL55712. The corresponding pA2 values were 6.3 +/- 0.3 (n = 10) for LTC4 and 5.7 +/- 0.2 (n = 6) for NMLTC4. In the presence of acivicin, a gamma-glutamyl transpeptidase inhibitor, the LTC4 concentration-response curve on trachea was displaced to the left, but the NMLTC4 curve was unaffected. The comparative potencies in the presence of acivicin on trachea indicate that LTC4 is approximately 6 times more potent than NMLTC4 whereas on ileum, in the presence of FPL55712 LTC4 is approximately 14 times more potent. In-vivo NMLTC4 is a weak bronchoconstrictor substance being 20-30 less potent than LTC4. However, unlike the in-vitro studies the bronchospasm was significantly reduced by pretreatment with LTD4 antagonists. NMLTC4 administered intravenously produced a pronounced hypertensive effect which appeared to be due to peripheral vasoconstriction.
N-甲基白三烯C4（NMLTC4）是白三烯C4的一种合成类似物，已被证明不是γ-谷氨酰转肽酶的底物。NMLTC4可使豚鼠回肠和气管收缩，其pD2值分别为7.7±0.12（n = 6）和8.1±0.1（n = 6），而白三烯C4的值分别为9.0±0.1（n = 5）和8.0±0.2（n = 6）。回肠上白三烯C4和NMLTC4的浓度-反应曲线被FPL55712向右移动。白三烯C4和NMLTC4相应的pA2值分别为6.3±0.3（n = 10）和5.7±0.2（n = 6）。在γ-谷氨酰转肽酶抑制剂阿西维辛存在的情况下，气管上白三烯C4的浓度-反应曲线向左移动，但NMLTC4曲线不受影响。在阿西维辛存在的情况下，气管上的比较效价表明白三烯C4的效力约为NMLTC4的6倍，而在回肠上，在FPL55712存在的情况下，白三烯C4的效力约为NMLTC4的14倍。在体内，NMLTC4是一种弱支气管收缩物质，其效力比白三烯C4低20 - 30倍。然而，与体外研究不同的是，用白三烯D4拮抗剂预处理可显著减轻支气管痉挛。静脉注射NMLTC4会产生明显的高血压作用，这似乎是由于外周血管收缩所致。
