Trace amines depress GABAB response in dopaminergic neurons by inhibiting G-βγ-gated inwardly rectifying potassium channels
Trace amines depress GABAB response in dopaminergic neurons by inhibiting G-βγ-gated inwardly rectifying potassium channels
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DOI：
10.1124/mol.104.007427
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Mercuri, NB
中科院分区：
文献类型：
--
作者：
Federici, M;Geracitano, R;Mercuri, NB
微量胺 (TA) 存在于中枢神经系统中，可上调儿茶酚胺的释放，并与成瘾、注意力缺陷/多动症、帕金森病和精神分裂症的发病机制有关。通过使用大鼠中脑切片中多巴胺能细胞的细胞内和膜片钳记录，我们报告了两种TA，β-苯乙胺（β-PEA）和酪胺（TYR）对GABA（B）介导的缓慢抑制性突触后电位和巴氯芬激活的外向电流的抑制突触后作用。 beta-PEA 和 TYR 激活 G 蛋白，干扰 GABA(B) 受体和 G-β γ 门控内向整流钾通道之间的偶联。这是首次证明 β-PEA 和 TYR 抑制中枢神经系统神经元的抑制性突触电位，支持它们作为神经调节剂的新兴作用。
Trace amines (TAs) are present in the central nervous system in which they up-regulate catecholamine release and are implicated in the pathogenesis of addiction, attention-deficit/hyperactivity disorder, Parkinson's disease, and schizophrenia. By using intracellular and patch-clamp recordings from dopaminergic cells in the rat midbrain slices, we report a depressant postsynaptic action of two TAs, beta-phenylethylamine (beta-PEA) and tyramine (TYR) on the GABA(B)-mediated slow inhibitory postsynaptic potential and baclofen-activated outward currents. beta-PEA and TYR activated G-proteins, interfering with the coupling between GABA(B) receptors and G-beta gamma-gated inwardly rectifying potassium channels. This is the first demonstration that beta-PEA and TYR depress inhibitory synaptic potentials in neurons of the central nervous system, supporting their emerging role as neuromodulators.