Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons.
Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons.
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DOI：
10.1111/j.1471-4159.2010.07059.x
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发表时间：
2010-12
影响因子：
4.7
通讯作者：
Alkayed NJ
中科院分区：
文献类型：
--
作者：
Iliff JJ;Fairbanks SL;Balkowiec A;Alkayed NJ
环氧二十碳三烯酸（Epoxyeicosatrienoicacids，ECOs）是由花生四烯酸经细胞色素P450环氧合酶催化合成的具有生物活性的类二十烷酸。我们先前描述了在大鼠三叉神经节神经元中表达的E2 - 2 J环氧合酶，并且E2 - 2 J信号传导参与血管周围神经刺激引起的脑血管扩张。在这里，我们评估的三叉神经节神经元中的E3信号通路的存在和它们的作用，调节降钙素基因相关肽（CGRP）的三叉神经节神经元的释放。液相色谱串联质谱法确定的存在下，每一个的四个Escherichia regio异构体内的初级三叉神经节神经元。用瞬时受体电位香草酸-1通道激动剂辣椒素（100 nmol/L）或去极化K+（60 mmol/L）刺激1小时，通过ELISA测量增加CGRP释放。14，15-环氧二十碳-5（Z）-烯酸（14，15-EEZE，10 μmol/L）预处理30 min可抑制CGRP的释放。K+刺激使CGRP释放增加到对照水平的2.9 ± 0.3倍，而在14，15-EEZE存在下，K+诱发的CGRP释放显著降低到对照释放的1.1 ± 0.2倍（p<0.01 ANOVA，n=6）。14，15-EEZE同样减弱辣椒素诱发的三叉神经节神经元的CGRP释放（p<0.05 ANOVA，n=6）。同样地，预先用β-环氧合酶抑制剂处理减弱了刺激诱发的CGRP释放。这些数据表明，肾上腺素是大鼠三叉神经节神经元的内源性成分，并表明它们可能作为神经肽释放的细胞内调节剂，这可能对治疗偏头痛，中风和蛛网膜下腔出血后血管痉挛具有重要的临床意义。
Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of CYP-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. Herein we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for one hour with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K+ (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K+ stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, while in the presence of 14,15-EEZE K+-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p<0.01 ANOVA, n=6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p<0.05 ANOVA, n=6). Similarly, pre-treatment with the CYP epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage.
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影响因子：
8.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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DOI：
10.1152/ajpheart.01211.2007
发表时间：
2008-08-01
影响因子：
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作者：
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通讯作者：
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