Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells

Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells
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DOI:
10.1016/j.mcn.2007.12.010
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发表时间:
2008-04-01
影响因子:
3.5
通讯作者:
Avila, J.
Avila, J.
中科院分区:
医学3区
文献类型:
--
作者:
Gomez-Ramos, A.;Diaz-Hernandez, M.;Avila, J.

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细胞外tau促进培养的神经元细胞内钙水平的增加。我们发现这种增加在毒蕈碱受体拮抗剂存在时受到损害。为了确定这些受体的性质,我们测试了不同特异性毒蕈碱受体拮抗剂对tau促进钙增加的影响。我们的研究结果表明,在毒蕈碱受体拮抗剂(主要是M1和M3)存在的情况下,这种增加不会发生。转染M1和M3毒蕈碱受体cDNA的神经元细胞在加入tau蛋白后,细胞内钙含量也没有类似的增加。这些结果表明,观察到的tau蛋白对神经元(神经母细胞瘤和海马和皮质神经元原代培养)细胞的作用是通过M1和M3毒蕈碱受体进行的。因此,通过使用特异性受体拮抗剂阻断M1和M3受体,可以防止tau病变中可能发生的tau毒性作用。(c) 2007爱思唯尔公司版权所有。
Extracellular tau promotes an increase in the level of intracellular calcium in cultured neuronal cells. We have found that such increase is impaired in the presence of antagonists of muscarinic receptors. In order to identify the nature of those receptors, we have tested the effect of different specific muscarinic receptor antagonists on tau promoted calcium increase. Our results indicate that the increase does not take place in the presence of antagonists of muscarinic (mainly M1 and M3) receptors. A similar increase in intracellular calcium was found in no neuronal cells transfected with cDNA of M1 and M3 muscarinic receptors when tau was added. These results suggest that observed effect of tau protein on neuronal (neuroblastoma and primary cultures of hippocampal and cortical neurons) cells is through M1 and M3 muscarinic receptors. Therefore blocking M1 and for M3 receptors, by using specific receptor antagonists, can prevent that tau toxic effect that could take place in tauopathies. (c) 2007 Elsevier Inc. All rights reserved.