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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes.
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Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes.

机译：喹啉酸刺激突触体谷氨酸释放并抑制谷氨酸摄入星形胶质细胞。

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摘要

Quinolinic acid (QA) is an endogenous neurotoxin involved in various neurological diseases, whose action seems to be exerted via glutamatergic receptors. However, the exact mechanism responsible for the neurotoxicity of QA is far from being understood. We have previously reported that QA inhibits vesicular glutamate uptake. In this work, investigating the effects of QA on the glutamatergic system from rat brain, we have demonstrated that QA (from 0.1 to 10mM) had no effect on synaptosomal L-[3H]glutamate uptake. The effect of QA on glutamate release in basal (physiological K+ concentration) or depolarized (40 mM KCl) conditions was evaluated. QA did not alter K+-stimulated glutamate release, but 5 and 10mM QA significantly increased basal glutamate release. The effect of dizolcipine (MK-801), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor on glutamate release was investigated. MK-801 (5 microM) did not alter glutamate release per se, but completely abolished the QA-induced glutamate release. NMDA (50 microM) also stimulated glutamate release, without altering QA-induced glutamate release, suggesting that QA effects were exerted via NMDA receptors. QA (5 and 10mM) decreased glutamate uptake into astrocyte cell cultures. Enhanced synaptosomal glutamate release, associated with inhibition of glutamate uptake into astrocytes induced by QA could contribute to increase extracellular glutamate concentrations which ultimately lead to overstimulation of the glutamatergic system. These data provide additional evidence that neurotoxicity of QA may be also related to disturbances on the glutamatergic transport system, which could result in the neurological manifestations observed when this organic acid accumulates in the brain.
机译：喹啉酸（QA）是一种内源性神经毒素，涉及多种神经系统疾病，其作用似乎是通过谷氨酸能受体发挥的。但是，导致QA神经毒性的确切机制尚不清楚。我们之前已经报道过QA抑制水泡谷氨酸的摄取。在这项工作中，研究了QA对大鼠大脑谷氨酸能系统的影响，我们证明了QA（从0.1到10mM）对突触体L- [3H]谷氨酸的摄取没有影响。评估了QA对基础（生理K +浓度）或去极化（40 mM KCl）条件下谷氨酸释放的影响。 QA不会改变K +刺激的谷氨酸释放，但是5和10mM QA会显着增加基础谷氨酸的释放。研究了N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂地佐洛辛（MK-801）对谷氨酸释放的影响。 MK-801（5 microM）本身不会改变谷氨酸盐的释放，但完全消除了QA诱导的谷氨酸盐的释放。 NMDA（50 microM）也刺激了谷氨酸的释放，而没有改变QA诱导的谷氨酸的释放，这表明QA的作用是通过NMDA受体发挥的。 QA（5和10mM）降低了星形胶质细胞培养物中谷氨酸的摄取。突触体谷氨酸盐释放的增强，与抑制QA诱导的星形胶质细胞吸收谷氨酸有关，可能有助于增加细胞外谷氨酸的浓度，最终导致对谷氨酸能系统的过度刺激。这些数据提供了其他证据，表明QA的神经毒性也可能与谷氨酸能转运系统的紊乱有关，当这种有机酸在大脑中积累时，这可能会导致观察到神经系统的表现。

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