通过环AMP依赖性蛋白激酶A调节大鼠背根神经节神经元中对loureirin B的抗河豚毒素钠电流的调节。,Journal of Cellular Biochemistry

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通过环AMP依赖性蛋白激酶A调节大鼠背根神经节神经元中对loureirin B的抗河豚毒素钠电流的调节。
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2019-10-23 , DOI: 10.1002/jcb.29414
Song Cheng _{1,

2,

3} , Yi Rong _{1,

2,

3} , Minjie Ma _{1,

2,

3} , Xianguang Lin _{1,

2,

3} , Xiangming Liu ₄ , Chenhong Li _{1,

2,

3} , Xiaofei Yang _{1,

2,

3} , Su Chen _{1,

2,

3}

Affiliation

为了研究卢西林B的调节机制，在大鼠背根神经节（DRG）神经元的抗河豚毒素（TTX-R）钠通道上从龙血树中提取了黄酮。基于膜片钳技术和分子生物学方法进行了实验。我们观察到了鼠李糖苷B对DRG神经元中TTX-R钠电流的时间依赖性抑制作用，发现占用理论和速率理论都不能很好地解释鼠李糖苷B对TTX-R钠电流的时间依赖性抑制作用。这表明第二信使介导的信号传导途径可能参与了调节机制。因此，通过ELISA试剂盒检测了在与loureirin B孵育前后DRG神经元的细胞周期蛋白AMP（cAMP）水平。结果表明，卢西瑞林B可以提高cAMP水平，而cAMP的升高是由卢瑞希林B诱导的腺苷酸环化酶（AC）增强引起的。免疫标记实验进一步证实，卢瑞希林B可以促进DRG神经元中PKA的产生。在存在PKA抑制剂H-89的情况下，逆向性输尿管苷B对TTX-R钠电流的抑制作用被逆转。Forskolin是一种提高cAMP水平的生化工具，它也可以减少类似于卢西里汀B的TTX-R钠电流。这些研究表明，卢西里汀B可以通过AC / cAMP调节DRG神经元中的TTX-R钠通道。 / PKA途径涉及AC和PKA的激活，这也可以用来解释卢蕾瑞林B的其他药理作用。免疫振铃实验进一步证实，鼠李糖素B可以促进DRG神经元中PKA的产生。在存在PKA抑制剂H-89的情况下，逆转了芦荟素B对TTX-R钠电流的抑制作用。Forskolin是一种提高cAMP水平的生化工具，它也可以减少类似于卢西林B的TTX-R钠电流。这些研究表明，卢西林B可以通过AC / cAMP调节DRG神经元中的TTX-R钠通道/ PKA途径涉及AC和PKA的激活，这也可以用来解释卢蕾瑞林B的其他药理作用。免疫振铃实验进一步证实，鼠李糖素B可以促进DRG神经元中PKA的产生。在存在PKA抑制剂H-89的情况下，逆向性输尿管苷B对TTX-R钠电流的抑制作用被逆转。Forskolin是一种提高cAMP水平的生化工具，它也可以减少类似于卢西里汀B的TTX-R钠电流。这些研究表明，卢西里汀B可以通过AC / cAMP调节DRG神经元中的TTX-R钠通道。 / PKA途径涉及AC和PKA的激活，这也可以用来解释卢蕾瑞林B的其他药理作用。

"点击查看英文标题和摘要"

Modulation on tetrodotoxin-resistant sodium current of loureirin B in rat dorsal root ganglion neurons via cyclic AMP-dependent protein kinase A.

To search the modulation mechanism of loureirin B, a flavonoid is extracted from Dracaena cochinchinensis, on tetrodotoxin-resistant (TTX-R) sodium channel in dorsal root ganglion (DRG) neurons of rats. Experiments were carried out based on patch-clamp technique and molecular biological methods. We observed the time-dependent inhibition of loureirin B on TTX-R sodium currents in DRG neurons and found that neither occupancy theory nor rate theory could well explain the time-dependent inhibitory effect of loureirin B on TTX-R sodium currents. It suggested that a second messenger-mediated signaling pathway may be involved in the modulation mechanism. So the cyclin AMP (cAMP) level of the DRG neurons before and after incubation with loureirin B was tested by ELISA Kit. Results showed that loureirin B could increase the cAMP level and the increased cAMP was caused by the enhancement of adenylate cyclase (AC) induced by loureirin B. Immunolabelling experiments further confirmed that loureirin B can promote the production of PKA in DRG neurons. In the presence of the PKA inhibitor H-89, the inhibitory effect of loureirin B on TTX-R sodium currents was reversed. Forskolin, a tool in biochemistry to raise the levels of cAMP, also could reduce TTX-R sodium currents similar to that of loureirin B. These studies demonstrated that loureirin B can modulate the TTX-R sodium channel in DRG neurons via an AC/cAMP/PKA pathway involving the activation of AC and PKA, which also can be used to explain the other pharmacological effects of loureirin B.

更新日期：2019-11-01

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