Epoxygenase metabolites of arachidonic acid affect electrophysiologic properties of rat tracheal epithelial cells1.
Epoxygenase metabolites of arachidonic acid affect electrophysiologic properties of rat tracheal epithelial cells1.
复制标题
DOI：
--
复制
发表时间：
1998-08
期刊：
影响因子：
--
通讯作者：
J. Pascual;A. McKenzie;J. Yankaskas;J. Falck;D. Zeldin
中科院分区：
文献类型：
--
作者：
J. Pascual;A. McKenzie;J. Yankaskas;J. Falck;D. Zeldin
环氧二碳三烯酸（EETs）和二羟基二十碳三烯酸是细胞色素P450花生四烯酸环氧化酶途径的产物，已被证明可以影响肾脏中的电解质运输；然而，这些化合物对气道上皮离子运输的影响尚未被研究。将完整的大鼠气管和大鼠气管上皮细胞原代培养物置于Ussing室中，监测在添加或不添加增加浓度(10（-9)-10(-6)M）的花生四烯酸、四种区域异构体eet中的每一种以及相应的二羟基二十碳三烯酸时，上皮电压（Vt）、短路电流（Isc）和电阻（Rt）的变化。在完整气管中，11,12- eet引起Vt和Isc的剂量依赖性降低（DeltaVt = 0）。在10(-6)M时，δ isc = -16.9 +/- 5.4 microA/cm2, P <。而Rt的变化与单独使用载体相比无显著差异。11,12-二羟基二碳三烯酸对Vt和Isc的影响较小，尽管花生四烯酸和其他化合物没有显著的影响。11,12-EET在浓度低至10(-9)m时，对培养的气管上皮细胞电参数也产生了类似的变化。11,12-EET的作用具有高度立体选择性，其活性仅限于11(R),12(S)-EET，这是最不丰富的大鼠肺对映体。阿米洛利预处理或粘膜暴露于无钠介质并没有显著改变11,12- eet诱导的Vt变化。相反，布美他尼预处理消除了11,12- eet的电生理效应，表明这些效应可能是通过抑制氯离子传导途径介导的。我们得出结论，花生四烯酸环氧化酶代谢物引起大鼠气道电参数的显著变化，并可能参与控制肺液和电解质的运输。
Epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids, products of the cytochrome P450 arachidonic acid epoxygenase pathway, have been shown to affect electrolyte transport in the kidney; however, the effects of these compounds on airway epithelial ion transport have not been investigated. Intact rat tracheas and primary cultures of rat tracheal epithelial cells were mounted in Ussing chambers to monitor changes in transepithelial voltage (Vt), short circuit current (Isc) and electrical resistance (Rt), with or without the addition of increasing concentrations (10(-9)-10(-6) M) of arachidonic acid, each of the four regioisomeric EETs and each of the corresponding dihydroxyeicosatrienoic acids. In intact tracheas, 11,12-EET caused dose-dependent decreases in Vt and Isc (DeltaVt = 0. 4 +/- 0.1 mV, DeltaIsc = -16.9 +/- 5.4 microA/cm2 at 10(-6) M, P < . 05 vs. vehicle), whereas changes in Rt were not significantly different than vehicle alone. 11,12-dihydroxyeicosatrienoic acid caused less impressive decreases in Vt and Isc, although arachidonic acid and the other compounds tested were without significant effects. 11,12-EET induced similar changes in cultured tracheal epithelial cell electrical parameters at concentrations as low as 10(-9) M. The effects of 11,12-EET were highly stereoselective, with activity limited to 11(R),12(S)-EET, the least abundant rat lung enantiomer. Pretreatment with amiloride or mucosal exposure to sodium free media did not significantly alter the 11,12-EET-induced changes in Vt. In contrast, pretreatment with bumetanide abolished the 11,12-EET electrophysiologic effects, suggesting that these effects may be mediated through inhibition of a chloride conductive pathway. We conclude that arachidonic acid epoxygenase metabolites cause significant changes in rat airway electrical parameters and may be involved in the control of lung fluid and electrolyte transport.