Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal monoamine release using in vivo microdialysis
Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal monoamine release using in vivo microdialysis
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DOI：
10.1038/sj.bjp.0704285
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发表时间：
2001-10-01
影响因子：
7.3
通讯作者：
Kaneko, S
中科院分区：
文献类型：
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作者：
Murakami, T;Okada, M;Kaneko, S
为了阐明卡马西平 (CBZ)、丙戊酸 (VPA) 和唑尼沙胺 (ZNS) 对神经递质胞吐作用影响的可能机制，通过微透析测定了这三种抗癫痫药物 (AED) 和肉毒毒素 (BoNT) 对基础、Ca2+- 和 K+ 诱发的多巴胺 (DA) 和血清素 (5-HT) 释放的相互作用。自由活动大鼠的海马。2 预显微注射突触融合蛋白抑制剂 BoNT/C 可以减少单胺的基础释放，但仅受到突触短蛋白抑制剂 BoNT/B 的微弱影响。 BoNT/C 选择性抑制 Ca2+ 诱发的释放。 K+ 诱发的释放主要被 BoNT/B 减少，而 BoNT/C 则微弱地减少。3 低浓度和高浓度的 CBZ 和 ZNS 灌注分别增加和减少基础单胺释放。 VPA 灌注可增加基础 5-HT 释放浓度依赖性，而基础 DA 释放则受 VPA 双相浓度依赖性影响，与 CBZ 和 ZNS 类似。 AED 对基础释放的刺激作用主要受到 BoNT/C 的抑制。4 低浓度的 CBZ、ZNS 和 VPA 会增加 Ca2+ 诱发的单胺释放，但高浓度时会降低。 AED 对 Ca2+ 诱发释放的这些作用被 BoNT/C 抑制，但不会被 BoNT/B 抑制。AED 浓度依赖性地减少 5 K+ 诱发的单胺释放。这三种 AED 对 K+ 诱发释放的抑制作用被 BoNT/B 抑制，但不被 BoNT/C 抑制，6 这些研究结果表明，CBZ、VPA 和 ZNS 的治疗相关浓度影响 DA 和 5-HT 的胞吐作用、静息阶段突触蛋白介导的单胺释放的增强以及去极化阶段突触短蛋白介导的释放的抑制。
I To elucidate possible mechanisms underlying the effects of carbamazepine (CBZ), valproate (VPA) and zonisamide (ZNS) on neurotransmitter exocytosis, the interaction between these three antiepileptic drugs (AEDs) and botulinum toxins (BoNTs) on basal, Ca2+- and K+-evoked release of dopamine (DA) and serotonin (5-HT) were determined by microdialysis in the hippocampus of freely moving rats.2 Basal release of monoamine was decreased by pre-microinjection of the syntaxin inhibitor, BoNT/C, but only weakly affected by the synaptobrevin inhibitor, BoNT/B. Ca2+-evoked release was inhibited by BoNT/C selectively. K+-evoked release was reduced by BoNT/B predominantly and BoNT/C weakly,3 Perfusion with low and high concentrations of CBZ and ZNS increased and decreased basal monoamine release, respectively. Perfusion with VPA increased basal 5-HT release concentration-dependently, whereas basal DA release was affected by VPA biphasic concentration-dependently, similar to CBZ and ZNS. This stimulatory action of AEDs on basal release was inhibited by BoNT/C predominantly.4 Ca2+-evoked monoamine release was increased by low concentrations of CBZ, ZNS and VPA, but decreased by high concentrations. These effects of the AEDs on Ca2+-evoked release were inhibited by BoNT/C, but not by BoNT/B.5 K+-evoked monoamine release was reduced by AEDs concentration-dependently. The inhibitory effect of these three AEDs on K+-evoked release was inhibited by BoNT/B, but not by BoNT/C,6 These findings suggest that the therapeutic-relevant concentration of CBZ, VPA and ZNS affects exocytosis of DA and 5-HT, the enhancement of syntaxin-mediated monoamine release during resting stage, and the inhibition of synaptobrevin-mediated release during depolarizing stage.