Crunelli Vincenzo, Di Giovanni Giuseppe
Rev Neurosci. 2014;25(2):195-206. doi: 10.1515/revneuro-2013-0059.
In recent years, it has become evident that many neurotransmitters and endogenous ligands differentially modulate synaptic γ-aminobutyric acid type A receptors (sGABAARs) and extrasynaptic GABAAR (eGABAARs). In this mini-review, we will summarize the available evidence on the ability of the monoamines serotonin (5-HT), noradrenaline (NA), and, in particular, dopamine (DA) to alter the functional response of eGABAARs, thus either increasing or decreasing tonic GABAA inhibition. Although this field of research is still in its infancy, it has already been demonstrated that eGABAARs show a nucleus-selective and neuronal-type-selective regulation by monoamines in a way that differs from that of sGABAARs. Further work will undoubtedly advance our knowledge of the intricate talk between monoamines and eGABAAR and may ultimately provide new leads for the treatment of neurological and neuropsychiatric disorders, where alteration in GABAAR function is one of the underlying causes.
近年来,许多神经递质和内源性配体对突触γ-氨基丁酸A型受体(sGABAARs)和突触外GABA受体(eGABAARs)的调节存在差异,这一点已变得很明显。在本综述中,我们将总结关于单胺类物质5-羟色胺(5-HT)、去甲肾上腺素(NA),尤其是多巴胺(DA)改变eGABAARs功能反应从而增强或减弱紧张性GABAA抑制作用的现有证据。尽管该研究领域仍处于起步阶段,但已经证明,eGABAARs受单胺类物质的调节具有核选择性和神经元类型选择性,其方式不同于sGABAARs。毫无疑问,进一步的研究将增进我们对单胺类物质与eGABAARs之间复杂相互作用的了解,并最终可能为治疗神经和神经精神疾病提供新线索,其中GABAAR功能改变是潜在病因之一。