Enhanced activity of GABA receptors inhibits glutamate release induced by focal cerebral ischemia in rat striatum |
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Authors: | Changhan Ouyang Lianjun Guo Qing Lu Xulin Xu Hongxing Wang |
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Institution: | 1. Departments of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China;2. Departments of Biochemistry, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China;3. Department of Pharmacology, Xianning College, Xianning 437100, PR China |
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Abstract: | Cerebral ischemia causes an excess release of glutamate, which can injure neurons. The striatum is one of the important regions vulnerable to hypoxia and ischemia. Using push–pull perfusion technique, we investigated the regulatory role of γ-aminobutyric acid (GABA) and its receptors in modifying the amount of glutamate in rat striatum with ischemia. Perfusion with exogenous GABA (1 mM) inhibited cerebral ischemia-induced glutamate release by as much as 47%. We further characterized relative roles of subtype receptors of GABA on glutamate release by using pharmacological tools. While baclofen (500 μM), a GABAB receptor agonist, suppressed ischemia-induced glutamate release by 52%, GABAB receptor antagonist saclofen (500 μM) failed to produce a significant increase of glutamate release. The GABAA receptor agonist muscimol (500 μM) also reduced by 38% the release of glutamate induced by cerebral ischemia but the GABAA receptor antagonist bicuculline (500 μM) had very little effect. The present study demonstrates that the excessive release of glutamate or the overly activated glutamate receptor, triggered by cerebral ischemia, can be down-regulated by exogenous GABA or by increased activity of GABA receptors, especially the presynaptic GABAB receptors, which might be one of the important mechanisms to protect against striatum neuronal damage from over stimulation by excessive glutamate during ischemia. |
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Keywords: | Cerebral ischemia GABA receptor Glutamate Push&ndash pull perfusion Rat striatum |
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