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Modification of presynaptic CaM kinase II affinity for ATP in hippocampus after long term blockade of serotonin reuptake

机译:长期阻断5-羟色胺再摄取后突触前突触前CaM激酶II对海马ATP的亲和力的改变

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Ca2+/calmodulin-dependent protein kinase II (CaMKII) is markedly enriched at synapses, where it is involved in the control of synaptic transmission, transmitter release and synaptic plasticity, CaMKII has also been found to be involved in the long-term action of antidepressants on post-receptor signaling mechanisms, because monoamine reuptake inhibitors induced an increase in autophosphorylation and activity of the kinase in nerve terminals of hippocampus, To study whether changes in the amount of enzyme or kinetic changes, due to posttranslational modifications, are responsible for kinase activation in nerve terminals, alpha-CaMKII level and kinetic constants of the autophosphorylation reaction as a function of ATP concentration were measured in presynaptic cytosol from hippocampus. Treatment with two serotonin reuptake inhibitors did not change the level of presynaptic kinase or the Vmax of autophosphorylation reaction. Instead the Km of the kinase for ATP was decreased 2.8-fold with fluvoxamine and 3.5-fold with paroxetine, implying an increase in the affinity for ATP, This result represents the first finding of changes in kinetic constants of a major brain enzyme after treatment with antidepressant drugs, (C) 2000 Elsevier Science Inc, All rights reserved. [References: 21]
机译:Ca2 + /钙调蛋白依赖性蛋白激酶II(CaMKII)在突触中显着富集,在此过程中,它参与突触传递,递质释放和突触可塑性的控制,还发现CaMKII参与抗抑郁药的长期作用关于受体后信号传导机制,因为单胺再摄取抑制剂引起海马神经末梢的自磷酸化和激酶活性增加,因此,研究翻译后修饰引起的酶量变化或动力学变化是否与激酶激活有关在神经末梢,在海马突触前细胞质中测量α-CaMKII水平和自磷酸化反应动力学常数与ATP浓度的关系。两种5-羟色胺再摄取抑制剂的治疗未改变突触前激酶的水平或自磷酸化反应的Vmax。相反,氟伏沙明使ATP激酶的Km降低2.8倍,帕罗西汀使ATP的Km降低3.5倍,这意味着对ATP的亲和力增加。这一结果代表了首次发现一种主要脑酶的动力学常数发生变化抗抑郁药,(C)2000 Elsevier Science Inc,保留所有权利。 [参考:21]

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