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首页> 外文期刊>American Journal of Physiology >Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries.
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Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries.

机译：内皮来源的2-花生四烯酸甘油：牛冠状动脉血管舒张性类花生酸释放的中间体。

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摘要

Acetylcholine stimulates the release of endothelium-derived arachidonic acid (AA) metabolites including prostacyclin and epoxyeicosatrienoic acids (EETs), which relax coronary arteries. However, mechanisms of endothelial cell (EC) AA activation remain undefined. We propose that 2-arachidonylglycerol (2-AG) plays an important role in this pathway. An AA metabolite isolated from bovine coronary ECs was identified as 2-AG by mass spectrometry. In ECs pretreated with the fatty acid amidohydrolase inhibitor diazomethylarachidonyl ketone (DAK; 20 micromol/l), methacholine (10 micromol/l)-stimulated 2-AG release was blocked by the phospholipase C inhibitor U-73122 (10 micromol/l) or the diacylglycerol lipase inhibitor RHC-80267 (40 micromol/l). In U-46619-preconstricted bovine coronary arterial rings, 2-AG relaxations averaging 100% at 10 micromol/l were inhibited by endothelium removal, by DAK, by the hydrolase inhibitor methyl arachidonylfluorophosphate (10 micromol/l), by the cyclooxygenase inhibitor indomethacin (10 micromol/l), but not by the CB1 cannabinoid receptor antagonist SR-141716 (1 micromol/l). The cytochrome P-450 inhibitor SKF-525a (10 micromol/l) and the 14,15-epoxyeicosa-5Z-enoic acid EET antagonist (14,15-EEZE; 10 micromol/l) further attenuated the indomethacin-resistant relaxations. The nonhydrolyzable 2-AG analogs noladin ether, 2-AG amide, and 14,15-EET glycerol amide did not induce relaxation. N-nitro-L-arginine-resistant relaxations to methacholine were also inhibited by U-73122, RHC-80267, and DAK. 14,15-EET glycerol ester increased opening of large-conductance K(+) channels 12-fold in cell-attached patches of isolated smooth muscle cells and induced relaxations averaging 95%. These results suggest that methacholine stimulates EC 2-AG production through phospholipase C and diacylglycerol lipase activation. 2-AG is further hydrolyzed to AA, which is metabolized to vasoactive eicosanoids. These studies reveal a role for 2-AG in EC AA release and the regulation of coronary tone.
机译：乙酰胆碱刺激内皮源性花生四烯酸（AA）代谢产物的释放，其中包括前列环素和环氧二十碳三烯酸（EETs），可放松冠状动脉。但是，内皮细胞（EC）AA激活的机制仍然不确定。我们建议2-花生四烯酸甘油酯（2-AG）在这一途径中发挥重要作用。从牛冠状动脉ECs分离的AA代谢物通过质谱鉴定为2-AG。在用脂肪酸酰胺水解酶抑制剂重氮甲基花生四烯酸酮（DAK; 20 micromol / l）预处理的ECs中，磷脂酶C抑制剂U-73122（10 micromol / l）阻断了乙酰甲胆碱（10 micromol / l）刺激的2-AG释放或二酰基甘油脂肪酶抑制剂RHC-80267（40微摩尔/升）。在U-46619预紧缩的牛冠状动脉环中，通过内皮去除，DAK，水解酶抑制剂甲基花生四烯酸氟磷酸酯（10 micromol / l），环氧化酶抑制剂吲哚美辛抑制了2-AG在10 micromol / l处平均100％的松弛。 （10 micromol / l），但不是由CB1大麻受体拮抗剂SR-141716（1 micromol / l）决定。细胞色素P-450抑制剂SKF-525a（10 micromol / l）和14,15-环氧-eicosa-5Z-烯酸EET拮抗剂（14,15-EEZE; 10 micromol / l）进一步减弱了对吲哚美辛的抵抗力。不可水解的2-AG类似物Noladin醚，2-AG酰胺和14,15-EET甘油酰胺不会引起松弛。 U-73122，RHC-80267和DAK也可抑制N-硝基-L-精氨酸对乙酰甲胆碱的松弛。 14,15-EET甘油酯增加大电导K（+）通道的打开，在分离的平滑肌细胞的细胞附着斑块中是12倍，并且诱导的平均松弛率为95％。这些结果表明，乙酰甲胆碱通过磷脂酶C和二酰基甘油脂酶活化来刺激EC 2-AG的产生。 2-AG被进一步水解为AA，并被代谢为血管活性类花生酸。这些研究揭示了2-AG在EC AA释放和冠状动脉张力调节中的作用。

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