1,2-naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea
1,2-naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea
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DOI：
10.1016/j.taap.2005.06.015
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发表时间：
2006-01-01
影响因子：
3.8
通讯作者：
Kumagai, Y
中科院分区：
文献类型：
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作者：
Kikuno, S;Taguchi, K;Kumagai, Y
1，2-萘醌（1，2-NQ）最近被确定为柴油机排气颗粒（DEP）和大气PW2.5中的环境醌。我们已经发现这种醌能够引起豚鼠气管平滑肌的浓度依赖性收缩，EC 50值为18.7 μ M。收缩需要细胞外钙，并抑制L-型钙通道阻滞剂硝苯地平和地尔硫卓。发现1，2-NQ激活磷脂酶A2（PLA 2）/脂氧合酶（LO）/香草素受体（VRI）信号。此外，1.2-NQ能够反式激活豚鼠气管中的蛋白酪氨酸激酶（PTKs），如表皮生长因子受体（EGFR），表明PTKs的磷酸化有助于1，2-NQ诱导的气管收缩。与这一观点一致，该作用被PTKs抑制剂染料木素和EGFR拮抗剂PDI 53035阻断，表明收缩至少部分归因于激活VRI的PTKs磷酸化，导致平滑肌细胞中细胞内钙含量增加。(c)2005年爱思唯尔公司All rights reserved.
1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PW2.5. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.7 mu M. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VRI) signaling. Additionally, 1.2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation of PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PDI53035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VRI, resulting in increased intracellular calcium content in the smooth muscle cells. (c) 2005 Elsevier Inc. All rights reserved.