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培养的小脑颗粒细胞中的谷氨酰胺转运

Glutamine transport in cerebellar granule cells in culture.

作者信息

Su T Z, Campbell G W, Oxender D L

机构信息

Department of Molecular Biology, Parke-Davis Pharmaceutical Research Division of Warner Lambert Co., Ann Arbor, MI 48105, USA.

出版信息

Brain Res. 1997 May 16;757(1):69-78. doi: 10.1016/s0006-8993(97)00139-x.

Abstract

In the present study, uptake of glutamine by rat cerebellar granule cells, a predominantly glutamatergic nerve cell population, has been investigated. Glutamine is taken up by granule cells via at least three transport systems, A, ASC and L. The L-type low affinity system (K(m) = 2.6 mM) is the major transport system in the absence of Na+. The systems A and ASC represent the Na(+)-dependent transport routes, both with almost identical high affinity for glutamine (K(m) = 0.26 mM). Similar transport systems for glutamine are also found in cerebral cortical neurons, a predominantly GABAergic nerve cell population, and cerebral cortical astrocytes. The glutamine transport properties in granule cells, however, show a series of differences from that of cortical neurons and astrocytes: (1) uptake of glutamine by granule cells is primarily mediated by system A (54%), while contributions by system A in cortical neurons and astrocytes are less than 30%; (2) granule cells exhibit strikingly higher transport efficiency for glutamine (V(max)/K(m) = 20 min(-1) for system A as compared to the V(max)/K(m) ratio of 5 min(-1) in cortical neurons and astrocytes), and (3) the initial uptake rates and the steady-state accumulation levels of glutamine are two- to threefold higher in granule cells than that of cortical neurons and astrocytes. These results taken together suggest that in accordance with the important need to replenish the neurotransmitter pool of glutamate, glutamatergic neurons exhibit highly efficient transport systems to accumulate glutamine, one of the major precursors of glutamate.

摘要

在本研究中,对大鼠小脑颗粒细胞(一种主要为谷氨酸能的神经细胞群体)摄取谷氨酰胺的情况进行了研究。谷氨酰胺通过至少三种转运系统(系统A、ASC和L)被颗粒细胞摄取。L型低亲和力系统(K(m)=2.6 mM)是在无钠离子情况下的主要转运系统。系统A和ASC代表钠离子依赖性转运途径,两者对谷氨酰胺的高亲和力几乎相同(K(m)=0.26 mM)。在大脑皮质神经元(一种主要为γ-氨基丁酸能的神经细胞群体)和大脑皮质星形胶质细胞中也发现了类似的谷氨酰胺转运系统。然而,颗粒细胞中的谷氨酰胺转运特性与皮质神经元和星形胶质细胞的转运特性存在一系列差异:(1)颗粒细胞摄取谷氨酰胺主要由系统A介导(54%),而系统A在皮质神经元和星形胶质细胞中的贡献小于30%;(2)颗粒细胞对谷氨酰胺表现出显著更高的转运效率(系统A的V(max)/K(m)=20 min(-1),相比之下皮质神经元和星形胶质细胞的V(max)/K(m)比值为5 min(-1)),以及(3)颗粒细胞中谷氨酰胺的初始摄取速率和稳态积累水平比皮质神经元和星形胶质细胞高两到三倍。综合这些结果表明,鉴于补充谷氨酸神经递质池的重要需求,谷氨酸能神经元表现出高效的转运系统来积累谷氨酰胺,谷氨酰胺是谷氨酸的主要前体之一。

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