Boulanger C M, Vanhoutte P M
INSERM, Hôpital Lariboisière, Paris, France.
J Vasc Res. 1997 May-Jun;34(3):175-85. doi: 10.1159/000159221.
Endothelial cells control the tone of the underlying smooth muscle by releasing relaxing factors (nitric oxide, NO, prostacyclin and endothelium-derived hyperpolarizing factor). G proteins couple a number of endothelial cell receptors to the activation of NO synthase. Pertussis toxin selectively ADP-ribosylates certain G proteins (mainly G(i)). In the porcine coronary artery, pertussis toxin inhibits the release of NO evoked by certain (serotonin, alpha2-adrenergic agonists, leukotrienes, thrombin), but not all, (bradykinin, adenosine diphosphate) endothelium-dependent vasodilators. This suggests that both G(i) and G(q) proteins can couple receptor activation to the increase in endothelial Ca2+ concentration required to stimulate NO synthase. In arteries with regenerated endothelium and in cultured endothelial cells, the release of NO evoked by pertussis-toxin-sensitive mechanisms is severely reduced or absent, while the response to other endothelium-dependent agonists is normal. To judge from experiments with cultured endothelial cells, the curtailment in pertussis-toxin-sensitive release of NO is due to an abnormal function rather than a reduced presence of G(i) proteins, or a reduced sensitivity of the cell membrane receptor. The selective impairment of G(i) proteins in regenerated endothelial cells predisposes the blood vessel wall to vasospasm and to the initiation of the atherosclerotic process.
内皮细胞通过释放舒张因子（一氧化氮、NO、前列环素和内皮衍生超极化因子）来控制其下方平滑肌的张力。G蛋白将一些内皮细胞受体与一氧化氮合酶的激活相偶联。百日咳毒素选择性地使某些G蛋白（主要是G(i)）发生ADP-核糖基化。在猪冠状动脉中，百日咳毒素抑制某些（5-羟色胺、α2-肾上腺素能激动剂、白三烯、凝血酶）而非所有（缓激肽、二磷酸腺苷）内皮依赖性血管舒张剂所诱发的NO释放。这表明G(i)蛋白和G(q)蛋白均可将受体激活与刺激一氧化氮合酶所需的内皮细胞Ca2+浓度升高相偶联。在具有再生内皮的动脉和培养的内皮细胞中，由百日咳毒素敏感机制诱发的NO释放严重减少或缺失，而对其他内皮依赖性激动剂的反应则正常。从培养内皮细胞的实验判断，百日咳毒素敏感的NO释放减少是由于功能异常，而非G(i)蛋白含量降低或细胞膜受体敏感性降低。再生内皮细胞中G(i)蛋白的选择性损伤使血管壁易发生血管痉挛和动脉粥样硬化进程的起始。
