Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University of Vienna Vienna, Austria.
Front Cell Neurosci. 2011 Jun 22;5:7. doi: 10.3389/fncel.2011.00007. eCollection 2011.
γ-Aminobutyric acid type A receptors (GABA(A)Rs) are the major inhibitory neurotransmitter receptors in the central nervous system, and importantly contribute to the functional regulation of the nervous system. Several studies in the last few decades have convincingly shown that GABA can be co-localized with other neurotransmitters in the same synapse, and can be co-released with these neurotransmitters either from the same vesicles or from different vesicle pools. The co-released transmitters may act on post-synaptically co-localized receptors resulting in a simultaneous activation of both receptors. Most of the studies investigating such co-activation observed a reduced efficacy of GABA for activating GABA(A)Rs and thus, a reduced inhibition of the post-synaptic neuron. Similarly, in several cases activation of GABA(A)Rs has been reported to suppress the response of the associated receptors. Such a receptor cross-talk is either mediated via a direct coupling between the two receptors or via the activation of intracellular signaling pathways and is used for fine tuning of inhibition in the nervous system. Recently, it was demonstrated that a direct interaction of different receptors might already occur in intracellular compartments and might also be used to specifically target the receptors to the cell membrane. In this article, we provide an overview on such cross-talks between GABA(A)Rs and several other neurotransmitter receptors and briefly discuss their possible physiological and clinical importance.
γ-氨基丁酸 A 型受体（GABA(A)Rs）是中枢神经系统中主要的抑制性神经递质受体，对神经系统的功能调节起着重要作用。过去几十年的几项研究令人信服地表明，GABA 可以在同一突触中与其他神经递质共存，并可以与这些神经递质一起从同一囊泡或不同的囊泡池中释放。共释放的递质可以作用于突触后共定位的受体，从而同时激活这两种受体。大多数研究共激活的观察到 GABA 激活 GABA(A)Rs 的功效降低，因此，对突触后神经元的抑制作用降低。同样，在几种情况下，激活 GABA(A)Rs 已被报道抑制相关受体的反应。这种受体串扰要么通过两个受体之间的直接偶联介导，要么通过激活细胞内信号通路介导，用于精细调节神经系统中的抑制作用。最近，已经证明不同受体之间的直接相互作用可能已经发生在细胞内区室中，并且也可能用于将受体特异性靶向细胞膜。在本文中，我们概述了 GABA(A)Rs 与几种其他神经递质受体之间的这种串扰，并简要讨论了它们可能的生理和临床重要性。
