Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens.
Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens.
复制标题
蛋白激酶抑制剂会减少伏隔核中 GABA 的释放，但不会减少谷氨酸的释放。
DOI：
10.1016/j.neuropharm.2007.09.004
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发表时间：
2007
影响因子：
4.7
通讯作者：
Hjelmstad,GregoryO
中科院分区：
文献类型：
--
作者：
Warrier,Ajithkumar;Hjelmstad,GregoryO
我们研究了内源性蛋白激酶活性在大鼠延髓脑片突触传递中的作用。异喹啉磺酰胺H-7（50μM），一种非选择性丝氨酸/苏氨酸蛋白激酶抑制剂，对体外分离的谷氨酸能EPSC没有影响。然而，它以剂量依赖性方式减少GABA的释放。选择性cAMP依赖性蛋白激酶抑制剂H-89、PKC抑制剂Bisindolylmaleimide-1或cGMP依赖性蛋白激酶抑制剂KT 5823不能模拟H-7的这种作用。然而，肌球蛋白轻链激酶（MLCK）抑制剂ML-7的浴应用，显着降低IPSC的振幅和部分闭塞的IPSC的减少后观察到浴应用H-7。这些结果表明，内源性蛋白激酶活性，特别是MLCK活性，调节GABA，但不谷氨酸释放，到中型棘神经元在延髓核。
We investigated the role of endogenous protein kinase activity on synaptic transmission in the rat nucleus accumbens slice. The isoquinolinesulfonamide H-7 (50μM), a non-selective serine/threonine protein kinase inhibitor, had no effect on pharmacologically isolated glutamatergic EPSCs. However, it reduced GABA release in a dose-dependent manner. This effect of H-7 was not mimicked by the selective cAMP-dependent protein kinase inhibitor H-89, the PKC inhibitor Bisindolylmaleimide-1, or the cGMP-dependent protein kinase inhibitor KT5823. However, bath application of the myosin light chain kinase (MLCK) inhibitor, ML-7, significantly reduced IPSC amplitudes and partially occluded the reduction in IPSCs observed following bath application of H-7. These results suggest that endogenous protein kinase activity, specifically MLCK activity, regulates GABA, but not glutamate release, onto medium spiny neurons in the nucleus accumbens.