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全身性给予N-甲基-D-天冬氨酸对大鼠海马CA1区和纹状体中通过微透析测量的细胞外牛磺酸水平的影响。

Effect of systemic administration of N-methyl-D-aspartic acid on extracellular taurine level measured by microdialysis in the hippocampal CA1 field and striatum of rats.

作者信息

Shibanoki S, Kogure M, Sugahara M, Ishikawa K

机构信息

Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan.

出版信息

J Neurochem. 1993 Nov;61(5):1698-704. doi: 10.1111/j.1471-4159.1993.tb09806.x.

Abstract

The extracellular concentrations of amino acids in the hippocampal CA1 field and striatum of conscious freely moving rats were monitored simultaneously by in vivo brain microdialysis using HPLC with electrochemical detection. Under basal conditions, aspartate, glutamate, glutamine, glycine, taurine, and alanine were detected, but gamma-aminobutyric acid was undetectable in both regions. Intraperitoneal injection of N-methyl-D-aspartic acid (NMDA; 10 mg/kg) caused a significant increase (three- to fivefold) in the taurine concentration in the dialysate obtained from both the hippocampal CA1 and striatum, whereas other amino acids (aspartate, glutamate, and alanine) did not show significant changes. Local application of NMDA (300 microM) to both regions via the dialysis probes also caused a similar increase (three- to fivefold) in both regions. Under infusion of hypertonic Ringer's solution containing 150 mM sucrose, the effect of NMDA on the level of taurine in both the regional dialysates was not affected. The effect of NMDA was totally reduced by intraperitoneal administration of MK-801 (0.3-1.0 mg/kg), a noncompetitive antagonist of NMDA receptors. Continuous infusion of DL-2-amino-5-phosphonovaleric acid (1.0 mM), a competitive antagonist of NMDA receptors, via the dialysis probes completely inhibited the effect of NMDA. These findings suggest that systemic administration of NMDA is effective as well as local administration into the brain and that NMDA receptors might be involved in the regulation of the extracellular taurine level in the brain without dependence on cell swelling.

摘要

通过使用带电化学检测的高效液相色谱法的体内脑微透析技术,同时监测清醒自由活动大鼠海马CA1区和纹状体中氨基酸的细胞外浓度。在基础条件下,检测到了天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸,但在这两个区域均未检测到γ-氨基丁酸。腹腔注射N-甲基-D-天冬氨酸(NMDA;10mg/kg)导致从海马CA1区和纹状体获得的透析液中牛磺酸浓度显著增加(三到五倍),而其他氨基酸(天冬氨酸、谷氨酸和丙氨酸)未显示出显著变化。通过透析探针将NMDA(300μM)局部应用于这两个区域也导致这两个区域出现类似的增加(三到五倍)。在输注含有150mM蔗糖的高渗林格氏溶液时,NMDA对两个区域透析液中牛磺酸水平的影响不受影响。NMDA的作用通过腹腔注射MK-801(0.3-1.0mg/kg)(一种NMDA受体的非竞争性拮抗剂)而完全被减弱。通过透析探针持续输注NMDA受体的竞争性拮抗剂DL-2-氨基-5-磷酸戊酸(1.0mM)完全抑制了NMDA的作用。这些发现表明,NMDA的全身给药和脑内局部给药一样有效,并且NMDA受体可能参与了脑内细胞外牛磺酸水平的调节,而不依赖于细胞肿胀。

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