N-acetylaspartylglutamate (NAAG) is the probable mediator of axon-to-glia signaling in the crayfish medial giant nerve fiber.
N-acetylaspartylglutamate (NAAG) is the probable mediator of axon-to-glia signaling in the crayfish medial giant nerve fiber.
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N-乙酰天冬氨酰谷氨酸 (NAAG) 可能是小龙虾内侧巨神经纤维中轴突到神经胶质信号传导的介质。
DOI：
10.1016/s0306-4522(01)00271-8
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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：
Gafurov,B;Urazaev,AK;Grossfeld,RM;Lieberman,EM
以往的研究表明，高频刺激或谷氨酸可引起神经胶质细胞超极化。我们现在报道它也是由含有谷氨酸的二肽N-乙酰天冬氨酸谷氨酸(NAAG)、它的非水解性类似物β-NAAG以及在NAAG降解酶谷氨酸羧肽酶II的有效抑制剂2-(膦甲基)-戊二酸(2-PMPA)的存在下由NAAG产生的。虽然谷氨酸有类似的作用，但NAAG水解的另一种假定产物N-乙酰天冬氨酸和天冬氨酸(在2-PMPA存在的情况下)一样，对神经胶质细胞膜电位没有影响。刺激、谷氨酸、NAAG、β-NAAG或NAAG加2-PMPA所引起的超极化可被代谢性谷氨酸受体拮抗剂S-α-乙基谷氨酸完全阻断，但不被代谢性谷氨酸受体拮抗剂I或III所改变。N-甲基-D-天冬氨酸受体拮抗剂MK801减少但不能消除谷氨酸、NAAG或刺激所产生的超极化。这些结果与前一篇论文的结果相结合，与NAAG可能是主要的轴突到胶质细胞信号转导因子的假设是一致的。当未受刺激的神经纤维被谷氨酸再摄取阻断剂半胱氨酸处理时，胶质细胞有轻微的超极化，在加入半胱氨酸之前用2-PMPA预处理可以显著减轻这种超极化。在50赫兹/5的S刺激中，半胱氨酸也有类似的作用。根据这些结果，我们认为在这些实验条件下，NAAG水解产生的谷氨酸出现在轴突周围间隙，可能参与了神经胶质细胞的超极化。
Glial cell hyperpolarization previously has been reported to be induced by high frequency stimulation or glutamate. We now report that it also is produced by the glutamate-containing dipeptide N-acetylaspartylglutamate (NAAG), by its non-hydrolyzable analog β-NAAG, and by NAAG in the presence of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a potent inhibitor of the NAAG degradative enzyme glutamate carboxypeptidase II. The results indicate that NAAG mimics the effect of nerve fiber stimulation on the glia. Although glutamate has a similar effect, the other presumed product of NAAG hydrolysis, N-acetylaspartate, is without effect on glial cell membrane potential, as is aspartylglutamate (in the presence of 2-PMPA). The hyperpolarization induced by stimulation, glutamate, NAAG, β-NAAG, or NAAG plus 2-PMPA is completely blocked by the Group II metabotropic glutamate receptor antagonist (S)-α-ethylglutamate but is not altered by antagonists of Group I or III metabotropic glutamate receptors. The N-methyl-D-aspartate receptor antagonist MK801 reduces but does not eliminate the hyperpolarization generated by glutamate, NAAG or stimulation. These results, in combination with those of the preceding paper, are consistent with the premise that NAAG could be the primary axon-to-glia signaling agent. When the unstimulated nerve fiber is treated with cysteate, a glutamate reuptake blocker, there is a small hyperpolarization of the glial cell that can be substantially reduced by pretreatment with 2-PMPA before addition of cysteate. A similar effect of cysteate is seen during a 50 Hz/5 s stimulation. From these results we suggest that glutamate derived from NAAG hydrolysis appears in the periaxonal space under the conditions of these experiments and may contribute to the glial hyperpolarization.