脑内的内源性γ-L-谷氨酰和β-L-天冬氨酰肽与兴奋性氨基酸能神经传递

Endogenous gamma-L-glutamyl and beta-L-aspartyl peptides and excitatory aminoacidergic neurotransmission in the brain.

作者信息

Varga V, Janáky R, Saransaari P, Oja S S

机构信息

Department of Biomedical Sciences, University of Tampere, Finland.

出版信息

Neuropeptides. 1994 Jul;27(1):19-26. doi: 10.1016/0143-4179(94)90012-4.

DOI:10.1016/0143-4179(94)90012-4

PMID:7969817

Abstract

The effects of gamma-L-glutamyl- and beta-L-aspartyl di- and tripeptides on glutamatergic neurotransmission were tested in vitro. Of the peptides, gamma-L-glutamylglutamate was the most effective inhibitor, comparable to glutamate, of both Na(+)-independent and Cl-/Ca(2+)-activated binding/transport of glutamate. gamma-L-glutamylglutamate was most effective in the midbrain and hypothalamus and gamma-L-glutamylaspartate in the hippocampus when tested on the Na(+)-independent binding. The Cl-/Ca(2+)-dependent binding/transport of glutamate was affected by gamma-glutamylaspartate most strongly in the hippocampus. gamma-L-glutamylglycine and beta-L-aspartylglycine moderately inhibited the Na(+)-dependent uptake of L-glutamate and D-aspartate while the other peptides were only weak inhibitors. Reduced and oxidized glutathione enhanced the uptake of L-glutamate. The K(+)-stimulated release of L-glutamate was enhanced by gamma-L-glutamylglutamate and -aspartate and the release of D-aspartate also by gamma-L-glutamylglycine. The results indicate that both pre- and postsynaptic events in glutamatergic neurotransmission are modulated by these endogenous acidic oligopeptides.

摘要

在体外测试了γ-L-谷氨酰基和β-L-天冬氨酰二肽及三肽对谷氨酸能神经传递的影响。在这些肽中，γ-L-谷氨酰谷氨酸是最有效的抑制剂，在谷氨酸的非Na⁺依赖性和Cl⁻/Ca²⁺激活的结合/转运方面与谷氨酸相当。在测试非Na⁺依赖性结合时，γ-L-谷氨酰谷氨酸在中脑和下丘脑最有效，而γ-L-谷氨酰天冬氨酸在海马体中最有效。谷氨酸的Cl⁻/Ca²⁺依赖性结合/转运在海马体中受γ-谷氨酰天冬氨酸的影响最强。γ-L-谷氨酰甘氨酸和β-L-天冬氨酰甘氨酸适度抑制L-谷氨酸和D-天冬氨酸的Na⁺依赖性摄取，而其他肽只是弱抑制剂。还原型和氧化型谷胱甘肽增强L-谷氨酸的摄取。γ-L-谷氨酰谷氨酸和γ-L-谷氨酰天冬氨酸增强K⁺刺激的L-谷氨酸释放，γ-L-谷氨酰甘氨酸也增强D-天冬氨酸的释放。结果表明，这些内源性酸性寡肽调节谷氨酸能神经传递中的突触前和突触后事件。