首页> 外文期刊>Life sciences >ROLE OF CYCLIC AMP DEPENDENT PROTEIN KINASE IN CANNABINOID RECEPTOR MODULATION OF POTASSIUM A-CURRENT IN CULTURED RAT HIPPOCAMPAL NEURONS
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ROLE OF CYCLIC AMP DEPENDENT PROTEIN KINASE IN CANNABINOID RECEPTOR MODULATION OF POTASSIUM A-CURRENT IN CULTURED RAT HIPPOCAMPAL NEURONS

机译:循环AMP相关蛋白激酶在培养大鼠海马神经元钾电流中大麻素受体调节中的作用

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Cannabinoid receptor agonists have been previously shown to enhance a potassium A-current (I-A) in cultured rat hippocampal neurons. This effect has been further demonstrated to be dependent on G-protein linkage to adenylyl cyclase and levels of intracellular cyclic AMP (cAMP). The present study extends this analysis to the involvement of cAMP-dependent protein kinase (PKA) in this cascade. Specific activators and inhibitors of PKA were shown to have differential effects on the voltage dependence of I-A. Specific activators of PKA produced a negative shift in voltage dependence of I-A, whereas PKA inhibitors produced a positive shift in I-A voltage dependence, the latter similar to that effected by the cannabinoid agonist WIN 55,212-2. Although the negative shift in I-A induced by PKA stimulation could be reversed by PKA inhibitors, the positive shift produced by the PKA inhibitors alone was only 50-60% of the cannabinoid-produced shift in I-A voltage dependence. This partial effect of PKA. inhibition was confirmed by biochemical assays in the same cultured neurons that showed a similar 50-60% decrement in in vitro protein phosphorylation produced by PKA inhibitors. Results are discussed in terms of a diffusible second messenger linkage of the cannabinoid receptor to the A-current channel via the role of protein phosphorylation in modulation of I-A. [References: 28]
机译:先前已显示大麻素受体激动剂可在培养的大鼠海马神经元中增强钾电流(I-A)。进一步证明了这种作用取决于与腺苷酸环化酶的G蛋白连接和细胞内环状AMP(cAMP)的水平。本研究将此分析扩展到了cAMP依赖性蛋白激酶(PKA)参与该级联反应。已显示PKA的特定活化剂和抑制剂对I-A的电压依赖性具有不同的影响。 PKA的特定活化剂在I-A电压依赖性上产生负向偏移,而PKA抑制剂在I-A电压依赖性上产生正向偏移,后者与大麻素激动剂WIN 55,212-2的作用类似。尽管PKA抑制剂可以逆转PKA刺激引起的I-A负迁移,但仅PKA抑制剂产生的正迁移仅是I-A电压依赖性大麻素产生的迁移的50-60%。 PKA的部分效果。在相同的培养神经元中,通过生化分析证实了抑制作用,该结果显示PKA抑制剂产生的体外蛋白质磷酸化程度降低了50-60%。关于大麻素受体通过蛋白质磷酸化对I-A的调节作用与大麻素电流通道之间的弥散性第二信使连接而讨论了结果。 [参考:28]

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