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通过脑内微透析监测巴氯芬诱导的、钙依赖性刺激大鼠海马体内D-[3H]天冬氨酸的释放。

Baclofen-induced, calcium-dependent stimulation of in vivo release of D-[3H]aspartate from rat hippocampus monitored by intracerebral microdialysis.

作者信息

Nielsen E O, Aarslew-Jensen M, Diemer N H, Krogsgaard-Larsen P, Schousboe A

机构信息

Department of Chemistry BC, Royal Danish School of Pharmacy, Copenhagen.

出版信息

Neurochem Res. 1989 Apr;14(4):321-6. doi: 10.1007/BF01000034.

DOI:10.1007/BF01000034
PMID:2761667
Abstract

The release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) was studied at high K+ (100 mM) and under ischemia in rats implanted with 0.3 mm diameter dialysis tubing through the hippocampus. The effect on the D-[3H]aspartate release of the two gamma-aminobutyric acid (GABA) agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) and (+/-)-beta-(p-chlorophenyl)GABA (baclofen), which specifically activate GABAA and GABAB receptors, respectively, was studied. Initial experiments employing HPLC analysis showed a coincident increase in the amounts of glutamate, aspartate and the amount of radioactivity following introduction of K+ (100 mM) or a period of ischemia suggesting that the D-[3H]aspartate labels the transmitter pools of the two amino acids under the present experimental conditions. The presence of 10 mM baclofen or 10 mM THIP in the perfusion medium did not inhibit ischemia induced D-[3H]aspartate release. On the contrary, 10 mM baclofen alone (but not 0.1 or 1 mM) in the perfusion medium induced release of D-[3H]aspartate in a calcium dependent manner, whereas 10 mM THIP had no significant releasing effect.

摘要

在通过海马体植入直径为0.3毫米透析管的大鼠中,研究了在高钾(100 mM)和缺血条件下D-[3H]天冬氨酸(用作内源性谷氨酸和天冬氨酸的示踪剂)的释放情况。研究了两种γ-氨基丁酸(GABA)激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇(THIP)和(±)-β-(对氯苯基)GABA(巴氯芬)对D-[3H]天冬氨酸释放的影响,它们分别特异性激活GABAA和GABAB受体。采用高效液相色谱分析的初步实验表明,在引入100 mM钾或一段缺血期后,谷氨酸、天冬氨酸的量以及放射性的量同时增加,这表明在当前实验条件下,D-[3H]天冬氨酸标记了这两种氨基酸的递质池。灌注介质中存在10 mM巴氯芬或

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