Glucose-regulated dopamine release from substantia nigra neurons

Glucose-regulated dopamine release from substantia nigra neurons
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DOI:
10.1016/s0006-8993(00)02573-7
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发表时间:
2000-08-25
期刊:
影响因子:
2.9
通讯作者:
Levin, BE
Levin, BE
中科院分区:
医学3区
文献类型:
--
作者:
Levin, BE

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葡萄糖通过作用于ATP敏感性钾通道(K-ATP)来调节黑质(SN)、多巴胺(DA)神经元活性和GABA轴突终末递质的释放。在这里,通过在雄性SD大鼠的SN和纹状体放置微透析探针来评估改变SN葡萄糖水平对纹状体DA释放的影响。通过SN探针反向透析20 mM葡萄糖可使纹状体DA流出量瞬时减少32%,45分钟后恢复到基线水平,尽管血糖水平保持不变。在50 mM葡萄糖输注过程中,纹状体DA流出量一过性增加50%,60min后恢复到基线水平。注射100 mM葡萄糖可使纹状体DA流出量短暂减少25%,随后持续增加50%。在100 mM葡萄糖输液中加入GABA(A)拮抗剂荷包牡丹碱(50 MM),外排能力进一步增加30%。在基础血糖水平:黑质荷包牡丹碱单独使纹状体DA外流增加31%,这表明GABA对DA神经元有紧张性的抑制输入。磺脲类药物格列吡嗪(50 MU M)可使纹状体DA释放短暂增加25%,加入荷包牡丹碱后这种作用持续存在。因此,纹状体DA的释放受到SN葡萄糖水平变化的影响。这一反应可能很好地反映了葡萄糖对黑质SN DA神经元和GABA轴突终末K-ATP通道活动的已知影响。这些相互作用可以提供一种机制,即葡萄糖调节与食物摄入有关的运动活动。(C)2000 Elsevier Science B.V.保留所有权利。
Glucose modulates substantia niga (SN) dopamine (DA) neuronal activity and GABA axon terminal transmitter release by actions on an ATP-sensitive potassium channel (K-ATP). Here, the effect of altering SN glucose levels on striatal DA release was assessed by placing microdialysis probes into both the SN and striatum of male Sprague-Dawley rats. Reverse dialysis of 20 mM glucose through the SN probes transiently decreased striatal DA efflux by 32% with a return to baseline after 45 min despite constant glucose levels. During 50 mM glucose infusion, striatal DA efflux increased transiently by 50% and returned to baseline after 60 min. Infusion of 100 mM glucose produced a transient 25% decrease in striatal DA efflux followed by a sustained 50% increase above baseline. Efflux increased by a further 30% when the GABA(A) antagonist bicuculline (50 mu M) was added to the 100 mM glucose infusate. At basal glucose levels: nigral bicuculline alone raised striatal DA efflux by 31% suggesting a tonic GABA inhibitory input to the DA neurons. The sulfonylurea glipizide (50 mu M) produced a transient 25% increase in striatal DA release that became sustained when bicuculline was added. Thus, striatal DA release is affected by changing SN glucose levels. This response may well reflect the known effect of glucose on K-ATP channel activity on both SN DA neurons and GABA axon terminals in the substantia nigra. These interactions could provide a mechanism whereby glucose modulates motor activity involved in food intake. (C) 2000 Elsevier Science B.V. All rights reserved.