20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle
20-HETE inotropic effects involve the activation of a nonselective cationic current in airway smooth muscle
复制标题
DOI：
10.1152/ajplung.00381.2002
复制
发表时间：
2003-09-01
影响因子：
4.9
通讯作者：
Rousseau, E
中科院分区：
文献类型：
--
作者：
Cloutier, M;Campbell, S;Rousseau, E
20-羟基二十碳四烯酸（20-HETE）控制多种机制，如血管活性、促有丝分裂和各种组织中的离子转运。我们的目标是量化20-HETE对气道平滑肌（ASM）电生理特性的影响。对豚鼠ASM进行的等长张力测量显示，20-HETE诱导剂量依赖性变力作用，EC 50值为1.5 μ M。这种变力性反应对PKC抑制剂GF-109203 X不敏感。持续的收缩，需要Ca 2+的进入，被部分阻断由100 μ M Gd 3+或1 μ M硝苯地平，揭示了参与非容量性Ca 2+的进入和L-型Ca 2+通道，分别。微电极测量表明，3 μ M 20-HETE使豚鼠ASM的膜电位去极化13 +/- 2 mV（n = 7），30 μ M 1-油酰基-2-乙酰基-sn-甘油也是如此。在没有上皮细胞的情况下也观察到去极化效应。膜片钳记录表明，1 μ M的20-HETE激活的非选择性阳离子内向电流，可能是由瞬时受体电位通道的激活支持。RT-PCR证实了在豚鼠ASM细胞中存在典型的瞬时受体电位mRNA。
20-Hydroxyeicosatetraenoic acid (20-HETE) controls several mechanisms such as vasoactivity, mitogenicity, and ion transport in various tissues. Our goal was to quantify the effects of 20-HETE on the electrophysiological properties of airway smooth muscle (ASM). Isometric tension measurements, performed on guinea pig ASM, showed that 20-HETE induced a dose-dependent inotropic effect with an EC50 value of 1.5 muM. This inotropic response was insensitive to GF-109203X, a PKC inhibitor. The sustained contraction, requiring Ca2+ entry, was partially blocked by either 100 muM Gd3+ or 1 muM nifedipine, revealing the involvement of noncapacitative Ca2+ entry and L-type Ca2+ channels, respectively. Microelectrode measurements showed that 3 muM 20-HETE depolarized the membrane potential in guinea pig ASM by 13 +/- 2 mV (n = 7), as did 30 muM 1-oleoyl-2-acetyl-sn-glycerol. Depolarizing effects were also observed in the absence of epithelium. Patch-clamp recordings demonstrated that 1 muM 20-HETE activated a nonselective cationic inward current that may be supported by the activation of transient receptor potential channels. The presence of canonical transient receptor potential mRNA was confirmed by RT-PCR in guinea pig ASM cells.