VASCULAR ENDOTHELIAL-CELLS SYNTHESIZE NITRIC-OXIDE FROM L-ARGININE
VASCULAR ENDOTHELIAL-CELLS SYNTHESIZE NITRIC-OXIDE FROM L-ARGININE
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DOI：
10.1038/333664a0
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发表时间：
1988-06-16
期刊：
影响因子：
64.8
通讯作者：
MONCADA, S
中科院分区：
文献类型：
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作者：
PALMER, RMJ;ASHTON, DS;MONCADA, S
血管内皮细胞释放的一氧化氮（NO）可使血管组织条松弛1，并抑制血小板聚集2和血小板粘附3，这归因于内皮源性松弛因子4。我们现在证明，NO可以合成L-精氨酸的猪主动脉内皮细胞培养。通过生物测定法5、荧光光谱法1或质谱法检测一氧化氮。输注L-精氨酸和L-瓜氨酸可可逆地增强缓激肽和钙离子载体A23187诱导的内皮细胞NO释放，但D-精氨酸或其他结构类似物则无此作用。用~（15）N标记的L-精氨酸进行的质谱研究表明，这种增强作用是由于L-精氨酸末端胍基氮原子形成NO所致。该反应的严格底物特异性表明，L-精氨酸是血管内皮细胞中NO合成的前体。
Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue1and for the inhibition of platelet aggregation2and platelet adhesion3attributed to endothelium-derived relaxing factor4. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Nitric oxide was detected by bioassay5, chemiluminescence1or by mass spectrometry. Release of NO from the endothelial cells induced by bradykinin and the calcium ionophore A23187 was reversibly enhanced by infusions of L-arginine and L-citrulline, but not D-arginine or other close structural analogues. Mass spectrometry studies using15N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The strict substrate specificity of this reaction suggests that L-arginine is the precursor for NO synthesis in vascular endothelial cells.