Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes
Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes
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DOI：
10.1002/glia.10243
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发表时间：
2003-08-01
期刊：
影响因子：
6.2
通讯作者：
Abbracchio, MP
中科院分区：
文献类型：
--
作者：
Brambilla, R;Cottini, L;Abbracchio, MP
先前的文献数据表明，通过选择性拮抗剂阻断A（2A）腺苷受体可在各种神经退行性疾病模型中产生保护作用。这种效应背后的机制在很大程度上仍然是未知的。由于已知过度反应性星形胶质细胞形成是神经退行性事件特征疾病中导致细胞死亡的一个因素，本研究旨在确定选择性a （2A）受体拮抗剂是否可以抵消碱性成纤维细胞生长因子（bFGF）在体外诱导的反应性星形胶质细胞形成，bFGF是该反应的典型触发因素。将原代大鼠纹状体星形胶质细胞暴露于选择性A（2A）拮抗剂SCH58261中，可在体外以浓度依赖性消除bFGF诱导的星形胶质细胞形成。这种效应也可以用化学上不相关的A（2A）拮抗剂KW-6002再现。选择性受体激动剂直接激活A（2A）腺苷受体本身并不足以诱导星形胶质细胞形成，这表明A（2A）受体需要与其他bfgf诱导的基因协同作用才能触发反应性星形胶质细胞的形成。这些结果提供了a （2A）受体拮抗剂在脑损伤模型中诱导神经保护的基础机制，并突出了这种腺苷受体亚型作为神经胶质反应药理调节的新靶点。(C) 2003 Wiley-Liss, Inc。
Previous literature data show that blockade of A(2A) adenosine receptors via selective antagonists induces protection in various models of neurodegenerative diseases. The mechanisms underlying this effect are still largely unknown. Since it is known that excessive reactive astrogliosis is a factor contributing to cell death in diseases characterized by neurodegenerative events, the present study has been aimed at determining whether selective A(2A) receptor antagonists can counteract the formation of reactive astrocytes induced in vitro by basic fibroblast growth factor (bFGF), a typical trigger of this reaction. Exposure of primary rat striatal astrocytes to the selective A(2A) antagonist SCH58261 resulted in concentration-dependent abolition of bFGF induction of astrogliosis in vitro. This effect could also be reproduced with the chemically unrelated A(2A) antagonist KW-6002. The direct activation of A(2A) adenosine receptors by selective receptor agonists was not sufficient per se to induce astrogliosis, suggesting that the A(2A) receptor needs to act in concert with other bFGF-induced genes to trigger the formation of reactive astrocytes. These results provide a mechanism at the basis of the neuroprotection induced by A(2A) receptor antagonists in models of brain damage and highlight this adenosine receptor subtype as a novel target for the pharmacological modulation of the gliotic reaction. (C) 2003 Wiley-Liss, Inc.