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首页> 外文期刊>The European Journal of Neuroscience >Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.
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Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.

机译：加巴喷丁和普瑞巴林对大鼠内脏突触中谷氨酸释放的双重影响。

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Abstract We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) in layer V neurons in slices of rat entorhinal cortex. Both drugs reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation of afferent inputs, suggesting a presynaptic effect to reduce glutamate release. The frequency of spontaneous EPSCs (sEPSCs) was concurrently reduced by GBP, further supporting a presynaptic action. There was no significant change in amplitude although a slight reduction was seen, particularly with gabapentin, which may reflect a reduction in the number of larger amplitude sEPSCs. When activity-independent miniature EPSCs were recorded in the presence of tetrodotoxin, both drugs continued to reduce the frequency of events with no change in amplitude. The reduction in frequency induced by gabapentin or pregabalin was blocked by application of the l-amino acid transporter substrate l-isoleucine. The results show that gabapentin and pregabalin, like other anticonvulsants, reduce glutamate release at cortical synapses. It is possible that this reduction is a combination of two effects: a reduction of activity-dependent release possibly via interaction with P/Q-type voltage-gated Ca channels, and a second action, as yet unidentified, occurring downstream of Ca influx into the presynaptic terminals.
机译：摘要我们最近发现，抗惊厥药苯妥英钠，拉莫三嗪和丙戊酸钠均可减少内嗅皮层突触中谷氨酸的释放。在本研究中，我们使用大鼠内脏皮质切片V层神经元的兴奋性突触后电流（EPSC）的全细胞膜片钳记录，确定了这种性质是否由加巴喷丁和普瑞巴林共有。两种药物均降低了传入输入的电刺激诱发的EPSC的振幅并增加了其对脉冲比，这表明突触前作用可减少谷氨酸的释放。 GBP同时降低了自发EPSC（sEPSC）的频率，进一步支持了突触前的作用。振幅没有明显变化，尽管观察到略有下降，尤其是加巴喷丁，这可能反映出较大振幅sEPSC数量的减少。当在河豚毒素的存在下记录了与活动无关的微型EPSC时，两种药物都继续降低事件发生的频率，而幅度没有变化。加巴喷丁或普瑞巴林诱导的频率降低可通过应用L-氨基酸转运蛋白底物L-异亮氨酸来阻止。结果表明，加巴喷丁和普瑞巴林与其他抗惊厥药一样，可减少皮层突触中谷氨酸的释放。这种减少可能是两种影响的组合：一种可能是通过与P / Q型电压门控Ca通道相互作用而减少的与活性有关的释放，另一种是目前尚未确定的作用，发生在Ca流入下游。突触前的终端。

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