Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers: implications for axon-glia signaling.
Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers: implications for axon-glia signaling.
复制标题
小龙虾神经纤维中释放的 N-乙酰天冬氨酰谷氨酸的清除机制：对轴突-神经胶质信号传导的影响。
DOI：
10.1016/s0306-4522(01)00393-1
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发表时间：
2001
期刊：
影响因子：
3.3
通讯作者：
Lieberman,EM
中科院分区：
文献类型：
--
作者：
Urazaev,AK;ButtramJr,JG;Deen,JP;Gafurov,BS;Slusher,BS;Grossfeld,RM;Lieberman,EM
与放射性标记谷氨酸或谷氨酰胺孵育的小龙虾神经纤维积累这些底物并合成放射性n -乙酰天冬氨酸（NAAG）。在刺激内侧巨神经纤维时，NAAG是释放的主要放射性代谢物。由于NAAG激活的神经胶质超极化与谷氨酸或轴突刺激通过同一受体激活的神经胶质超极化相当，我们提出它可能是内侧巨轴突与其轴突周围胶质之间相互作用的中介。本文报道了naag信号活性终止的可能机制的研究。未受刺激的小龙虾巨大轴突及其相关胶质细胞在30分钟的孵育过程中没有从盐水中积累n -乙酰天冬氨酸[3H]。在孵育的最后一分钟以50hz的频率刺激中枢神经索，可显著增加内侧巨轴突及其相关胶质细胞中放射性标记谷氨酸、NAAG和谷氨酰胺的水平。这些结果表明，刺激敏感肽水解和代谢循环的放射性标记谷氨酸发生。在中枢神经纤维膜组分中存在β-NAAG-、半qualate-和2-(phosphomonomethyl)-pentanedioic acid-抑制性谷氨酸羧肽酶II活性，而在轴突和胶质细胞质组分中不存在。MK801对n -甲基- d -天冬氨酸（NMDA）受体的抑制或2-（磷甲乙基）-戊二酸对该酶的失活可减少高频刺激激活的神经胶质超极化。这些结果表明，轴突到神经胶质的信号被NAAG水解终止，形成的谷氨酸部分通过激活NMDA受体参与神经胶质电反应。NAAG的释放和谷氨酸羧肽酶II活性的增加似乎都是由神经刺激引起的。
Crayfish nerve fibers incubated with radiolabeled glutamate or glutamine accumulate these substrates and synthesize radioactive N-acetylaspartylglutamate (NAAG). Upon stimulation of the medial giant nerve fiber, NAAG is the primary radioactive metabolite released. Since NAAG activates a glial hyperpolarization comparable to that initiated by glutamate or axonal stimulation through the same receptor, we have proposed that it is the likely mediator of interactions between the medial giant axon and its periaxonal glia. This manuscript reports investigations of possible mechanisms for termination of NAAG-signaling activity. N-acetylaspartyl-[3H]glutamate was not accumulated from the bath saline by unstimulated crayfish giant axons or their associated glia during a 30-min incubation. Stimulation of the central nerve cord at 50 Hz during the last minute of the incubation dramatically increased the levels of radiolabeled glutamate, NAAG, and glutamine in the medial giant axon and its associated glia. These results indicate that stimulation-sensitive peptide hydrolysis and metabolic recycling of the radiolabeled glutamate occurred. There was a β-NAAG-, quisqualate- and 2-(phosphonomethyl)-pentanedioic acid-inhibitable glutamate carboxypeptidase II activity in the membrane fraction of central nerve fibers, but not in axonal or glial cytoplasmic fractions. Inactivation of this enzyme by 2-(phosphonomethyl)-pentanedioic acid or inhibition of N-methyl-D-aspartate (NMDA) receptors by MK801 reduced the glial hyperpolarization activated by high-frequency stimulation. These results indicate that axon-to-glia signaling is terminated by NAAG hydrolysis and that the glutamate formed contributes to the glial electrical response in part via activation of NMDA receptors. Both NAAG release and an increase in glutamate carboxypeptidase II activity appear to be induced by nerve stimulation.