Mechanisms leading to adenosine-stimulated proliferation of microvascular endothelial cells.
Mechanisms leading to adenosine-stimulated proliferation of microvascular endothelial cells.
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DOI：
10.1152/ajpheart.1990.258.1.h198
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
C. Meininger;H. Granger
中科院分区：
文献类型：
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作者：
C. Meininger;H. Granger
本研究探讨腺苷刺激微血管内皮细胞增殖的机制。代谢副产物腺苷、肌苷和次黄嘌呤不能刺激增殖。当腺苷的摄取被阻止时，对增殖的刺激没有改变，这表明腺苷的摄取并随后并入核苷酸库并不是增加增殖的机制。用腺苷类似物处理内皮细胞，可能对A1或A2受体有选择性，同样刺激了增殖。这表明腺苷3′，5′-环单磷酸腺苷（cAMP）可能不介导对腺苷的增殖反应。然而，用任何类似物处理后的细胞提取物的放射免疫分析显示cAMP增加。此外，用2',5'-二脱氧腺苷阻断腺苷酸环化酶可阻止这些类似物引起的增殖反应。这些数据表明，对腺苷的增殖反应取决于cAMP的增加。2小时霍乱毒素脉冲刺激内皮细胞增殖，进一步支持cAMP的作用。百日咳毒素预处理内皮细胞阻断了对增殖的刺激，表明Gi或类似的G蛋白也参与了增殖。我们得出结论，对腺苷的增殖反应涉及百日咳毒素敏感底物以及cAMP的增加。
This study investigated the mechanisms by which adenosine stimulates proliferation of microvascular endothelial cells. The metabolic byproducts of adenosine, inosine and hypoxanthine were unable to stimulate proliferation. When adenosine uptake was prevented, the stimulation of proliferation was unchanged, suggesting that uptake of adenosine with subsequent incorporation into the nucleotide pool is not the mechanism for increasing proliferation. Treatment of endothelial cells with adenosine analogues, presumably selective for either the A1 or A2 receptor, stimulated proliferation equally. This suggested that adenosine 3', 5'-cyclic monophosphate (cAMP) might not mediate the proliferative response to adenosine. However, radioimmunoassay of cell extracts after treatment with either analogue showed an increase in cAMP. In addition, adenylate cyclase blockade with 2', 5'-dideoxyadenosine prevented the proliferative response brought about by these analogues. These data suggest that the proliferative response to adenosine depends on an increase in cAMP. A 2-h pulse of cholera toxin stimulated endothelial cell proliferation, further supporting a role for cAMP. Pretreatment of endothelial cells with pertussis toxin blocked the stimulation of proliferation, indicating that a Gi or similar G protein is also involved in proliferation. We conclude that the proliferative response to adenosine involves a pertussis toxin-sensitive substrate as well as an increase in cAMP.