白三烯在气道平滑肌中的作用：钙依赖性及维拉帕米的抑制作用

Leukotriene effect in airways smooth muscle: calcium dependency and verapamil inhibition.

作者信息

Weiss E B, Mullick P C

出版信息

Prostaglandins Leukot Med. 1983 Sep;12(1):53-66. doi: 10.1016/0262-1746(83)90067-7.

Abstract

The extracellular calcium (Ca++) E dependency of the synthetic leukotrienes (LT) C4, D4 and E4 and inhibition of LTC4 by verapamil was demonstrated on guinea pig trachealis in vitro. LTC4 exhibited an intrinsic potency 170 X greater than histamine. Tension development by LTC4, D4 and E4 was equipotent at 2.5 mM (Ca++)E. Tension studies in 0.5 mM (Ca++)E indicate these three leukotrienes to be (Ca++)E dependent with a potency ranking of LTC4 greater than LTD4 and LTE4 (P less than 0.05 and P less than 0.001 respectively). Inhibition of LTC4 by verapamil yielded an IC50 of approximately 1.1 X 10(-4)M with complete inhibition at 2.2 X 10(-4)M; this antagonism was non-competitive. The specific dependency of verapamil inhibition of LTC4 to (Ca++)E was demonstrated by reversal of verapamil antagonism with 5.0 mM (Ca++)E. Synthetic leukotrienes C4, D4 and E4 are dependent upon (Ca++)E for their myotropic activity, an action non-competitively inhibited by the calcium channel blocker verapamil.

摘要

在豚鼠离体气管上证实了合成白三烯（LT）C4、D4和E4的细胞外钙（Ca++）E依赖性以及维拉帕米对LTC4的抑制作用。LTC4表现出比组胺大170倍的内在效力。在2.5 mM（Ca++）E时，LTC4、D4和E4引起的张力变化具有同等效力。在0.5 mM（Ca++）E下进行的张力研究表明，这三种白三烯具有（Ca++）E依赖性，效力排序为LTC4＞LTD4＞LTE4（分别为P＜0.05和P＜0.001）。维拉帕米对LTC4的抑制作用产生的IC50约为1.1×10−4M，在2.2×10−4M时完全抑制；这种拮抗作用是非竞争性的。通过用5.0 mM（Ca++）E逆转维拉帕米的拮抗作用，证实了维拉帕米对LTC4的抑制作用对（Ca++）E的特异性依赖性。合成白三烯C4、D4和E4的致肌活性依赖于（Ca++）E，钙通道阻滞剂维拉帕米可非竞争性抑制这一作用。