Glucocorticoids modulate neurotransmitter-induced glycogen metabolism in cultured cortical astrocytes
Glucocorticoids modulate neurotransmitter-induced glycogen metabolism in cultured cortical astrocytes
复制标题
DOI：
10.1046/j.1471-4159.2003.02235.x
复制
发表时间：
2004-02-01
影响因子：
4.7
通讯作者：
Magistretti, PJ
中科院分区：
文献类型：
--
作者：
Allaman, I;Pellerin, L;Magistretti, PJ
糖皮质激素(GC)被认为是外周组织中糖原稳态的关键调节剂，但它们在中枢神经系统中的作用仅有部分特征。地塞米松(DEX)可浓度依赖性地抑制去甲肾上腺素(NA)诱导的糖原合成，IC50为4.88 nM，最大抑制率为51%。这种作用是通过糖皮质激素受体(GRs)介导的，因为它被糖皮质激素类似物RU28362(100 NM)模拟，并被GR拮抗剂RU38486(1um)阻止。Dex不是通过改变信号转导机制发挥作用的，因为去甲肾上腺素能刺激引起的cAMP的形成没有变化。此外，当地塞米松联合应用或仅在短暂的NA应用后应用时，糖原合成受到相同程度的抑制。在NA存在的情况下，DEX既不改变[H-3]2-脱氧葡萄糖的摄取，也不改变乳酸的释放，这表明糖原合成的抑制不是葡萄糖利用或可获得性降低的结果。有趣的是，在地塞米松的存在下，NA诱导的糖原合成酶活性的增强被抑制(-27%)。这些结果表明，GC可能对神经能量学有重大影响，因为它们可以调节脑糖原代谢中与活动相关的变化。
Glucocorticoids (GC) are considered as key modulators of glycogen homeostasis in peripheral tissues, but their role in the central nervous system has only partially been characterized. Exposure of primary cultures of cortical astrocytes to dexamethasone (DEX), a synthetic glucocorticoid, results in the reduction of noradrenaline (NA)-induced glycogen synthesis in a concentration-dependent manner with a IC50 of 4.88 nM and a maximum inhibition of 51%. Such an effect is mediated via glucocorticoid receptors (GRs), since it is mimicked by the glucocorticoid analogue RU28362 (100 nM) and prevented by the GR antagonist RU38486 (1 muM). DEX does not act through alteration of signal transduction mechanisms, as cAMP formation induced by noradrenergic stimulation was unchanged. Moreover, glycogen synthesis was inhibited to the same extent when DEX was applied either together or only after a brief NA application. Neither [H-3]2-deoxyglucose uptake nor lactate release was altered by DEX in the presence of NA, demonstrating that inhibition of glycogen synthesis is not a consequence of reduced glucose utilization or availability. Interestingly, enhancement of glycogen synthase activity induced by NA was reduced in the presence of DEX (-27%). These results suggest that GC could have a significant influence on neuroenergetics as they could modulate activity-related changes in brain glycogen metabolism.