PKC links Gq-coupled receptors to DAT-mediated dopamine release
PKC links Gq-coupled receptors to DAT-mediated dopamine release
复制标题
DOI：
10.1111/j.1471-4159.2010.06788.x
复制
发表时间：
2010-07-01
影响因子：
4.7
通讯作者：
Falkenburger, Bjoern H.
中科院分区：
文献类型：
--
作者：
Opazo, Felipe;Schulz, Joerg B.;Falkenburger, Bjoern H.
多巴胺转运蛋白（DAT）介导许多脑区的多巴胺摄取，并被认为是黑质网状部多巴胺释放的基础。这种释放调节基底神经节输出和运动性能。它是由丘脑底核神经传入神经触发的。我们在这里表明，（G（q）-耦合）组I代谢型谷氨酸受体的激活足以诱导大鼠黑质网状部脑片多巴胺的释放。通过电流分析法测量释放并通过DAT拮抗剂抑制。在DAT表达细胞系中，多巴胺的释放可以通过G（q）偶联的毒蕈碱受体的激活来诱导。通过HPLC测量释放并通过DAT拮抗剂抑制。在这两种范式中，蛋白激酶C（PKC）的激活对于多巴胺释放都是必要且充分的，这表明G（q）偶联受体可以通过PKC诱导DAT介导的多巴胺释放，并为已知的调节提供了生理作用PKC介导的DAT释放。毒蕈碱受体和PKC的激活也诱导从表达去甲肾上腺素转运蛋白的细胞系释放，表明转运介导的释放可能与进一步的脑区相关。
P>The dopamine transporter (DAT) mediates dopamine uptake in many brain areas and has been suggested to underlie dopamine release in the substantia nigra pars reticulata. This release modulates basal ganglia output and motor performance. It is triggered by glutamatergic subthalamic afferents. We show here that activation of (G(q)-coupled) group I metabotropic glutamate receptors are sufficient to induce dopamine release in rat substantia nigra pars reticulata slices. Release was measured by amperometry and inhibited by a DAT antagonist. In a DAT-expressing cell line, dopamine release could be induced by activation of G(q)-coupled muscarinic receptors. Release was measured by HPLC and inhibited by a DAT antagonist. In both paradigms, activation of protein kinase C (PKC) was necessary and sufficient for dopamine release, suggesting that G(q)-coupled receptors can induce DAT-mediated dopamine release through PKC, and providing a physiological role for the known regulation of DAT-mediated release by PKC. Activation of muscarinic receptors and PKC also induced release from a cell line expressing the norepinephrine transporter, suggesting that transport-mediated release might be relevant in further brain areas.