Università degli Studi di Roma "Tor Vergata," Rome, Italy.
Front Syst Neurosci. 2011 Jul 4;5:56. doi: 10.3389/fnsys.2011.00056. eCollection 2011.
Trace amines (TAs) are a class of endogenous compounds strictly related to classic monoamine neurotransmitters with regard to their structure, metabolism, and tissue distribution. Although the presence of TAs in mammalian brain has been recognized for decades, until recently they were considered to be by-products of amino acid metabolism or as "false" neurotransmitters. The discovery in 2001 of a new family of G-protein-coupled receptors (GPCRs), namely trace amines receptors, has re-ignited interest in TAs. In particular, two members of the family, trace amine receptor 1 (TA(1)) and trace amine receptor 2 (TA(2)), were shown to be highly sensitive to these endogenous compounds. Experimental evidence suggests that TAs modulate the activity of catecholaminergic neurons and that TA dysregulation may contribute to neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, depression and Parkinson's disease, all of which are characterized by altered monoaminergic networks. Here we review recent data concerning the electrophysiological effects of TAs on the activity of mesencephalic dopaminergic neurons. In the context of recent data obtained with TA(1) receptor knockout mice, we also discuss the mechanisms by which the activation of these receptors modulates the activity of these neurons. Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABA(B) receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA(1) receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. While the first two effects have been well documented in our laboratory, the direct activation of GIRK channels by TA(1) receptors has been reported by others, but has not been seen in our laboratory (Geracitano et al., 2004). Further research is needed to address this point, and to further characterize the mechanism of action of TAs on dopaminergic neurons.
痕量胺（TAs）是一类与经典单胺神经递质在结构、代谢和组织分布上密切相关的内源性化合物。尽管哺乳动物大脑中存在 TAs 已经被认识了几十年，但直到最近，它们才被认为是氨基酸代谢的副产物或“假”神经递质。2001 年发现了一类新的 G 蛋白偶联受体（GPCRs），即痕量胺受体，这重新引起了人们对 TAs 的兴趣。特别是该家族的两个成员，痕量胺受体 1（TA1）和痕量胺受体 2（TA2），被证明对这些内源性化合物高度敏感。实验证据表明，TAs 调节儿茶酚胺能神经元的活性，而 TAs 失调可能导致神经精神疾病，包括精神分裂症、注意缺陷多动障碍、抑郁症和帕金森病，所有这些疾病的特征都是单胺能网络的改变。在这里，我们综述了最近关于 TAs 对中脑多巴胺能神经元活性的电生理效应的研究数据。在最近用 TA1 受体敲除小鼠获得的数据的背景下，我们还讨论了这些受体的激活调节这些神经元活性的机制。TAs 作用的三个重要新方面最近出现了：（a）由于多巴胺释放增加而导致的放电抑制；（b）减少 D2 和 GABA（B）受体介导的抑制反应（由于去抑制而产生的兴奋作用）；（c）TA1 受体直接激活 GIRK 通道，导致细胞膜超极化。虽然前两个效应在我们的实验室中得到了很好的证明，但 TA1 受体对 GIRK 通道的直接激活已被其他人报道，但在我们的实验室中尚未见到（Geracitano 等人，2004 年）。需要进一步的研究来解决这一点，并进一步表征 TAs 对多巴胺能神经元的作用机制。
