Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, α-(methylamino)isobutyrate
Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, α-(methylamino)isobutyrate
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DOI：
10.1111/j.1471-4159.2004.02478.x
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发表时间：
2004-07-01
影响因子：
4.7
通讯作者：
Ross, BD
中科院分区：
文献类型：
--
作者：
Kanamori, K;Ross, BD
清醒大鼠皮质纹状体区细胞外液中谷氨酰胺的基础浓度[Gln(ECF)]为385+/-16um。通过测量在几种流速(0.2-4微升/分钟)下收集的透析液中的谷氨酰胺浓度，并外推到零流速下的浓度，来确定该体内浓度。透析液中谷氨酰胺在躯体感觉皮质、海马和丘脑中的浓度差异无统计学意义。在这些脑区，当灌流50-250mMalpha-(甲氨基)异丁酸酯(MeAIB)时，[Gln(ECF)]升高了1.5-1.8倍。MeAIB是A系统氨基酸转运体摄取谷氨酰胺的竞争性抑制剂。结果表明，MeAIB可引起体内脑谷氨酸氨基转移酶(ECF)升高。MeAIB诱导的[Gln(ECF)]升高支持了目前的观点，即A系统Gln转运体(Gln T/SAT 1)是神经元摄取Gln(ECF)的主要途径，而神经胶质细胞释放Gln主要是由系统N转运体(SN1)介导的，而SN1不受MeAIB的抑制。本研究报道的稳态谷氨酰胺(ECF)浓度和MeAIB在体内抑制神经元摄取谷氨酰胺的有效性，与已知的谷氨酰胺转运体的体外动力学特性相结合，将有助于研究谷氨酰胺在完整脑中的转运。
The basal concentration of glutamine in the extracellular fluid, [GLN(ECF)], was determined to be 385 +/- 16 muM in the cortico-striatal region of awake rats. This in vivo concentration was determined by measuring glutamine concentrations in dialysates collected at several flow rates (0.2-4 muL/min), and extrapolating to the concentration at zero flow-rate. Dialysate glutamine concentrations in the somatosensory cortex, hippocampus and thalamus showed no statistically significant difference. In these brain regions, [GLN(ECF)] was elevated 1.5- to 1.8-fold upon perfusion of 50-250 mMalpha-(methylamino)isobutyrate (MeAIB), a competitive inhibitor of glutamine uptake by system A amino acid transporter. The results show, for the first time, that MeAIB causes elevation of brain GLN(ECF)in vivo. The MeAIB-induced elevation of [GLN(ECF)] provides additional support for the current view that system A GLN transporter (Gln T/SAT 1) is the major pathway for the uptake of GLN(ECF) by neurons, while GLN release from glia is mainly mediated by a system N transporter (SN1) which is not inhibitable by MeAIB. The steady-state GLN(ECF) concentration and the effectiveness of MeAIB in inhibiting neuronal GLN uptake in vivo, reported in this study, will be useful, when combined with the known in vitro kinetic properties of the GLN transporters, for study of GLN transport in the intact brain.