Łątka Kamil, Jończyk Jakub, Bajda Marek
Jagiellonian University Medical College, Faculty of Pharmacy, Department of Physicochemical Drug Analysis, 30-688 Cracow, Medyczna 9, Poland.
Jagiellonian University Medical College, Faculty of Pharmacy, Department of Physicochemical Drug Analysis, 30-688 Cracow, Medyczna 9, Poland.
Int J Biol Macromol. 2020 Apr 30. doi: 10.1016/j.ijbiomac.2020.04.126.
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the nervous system. It plays a crucial role in many physiological processes. Upon release from the presynaptic element, it is removed from the synaptic cleft by reuptake due to the action of GABA transporters (GATs). GATs belong to a large SLC6 protein family whose characteristic feature is sodium-dependent relocation of neurotransmitters through the cell membrane. GABA transporters are characterized in many contexts, but their spatial structure is not fully known. They are divided into four types, which differ in occurrence and role. Herein, the special attention was paid to these transporting proteins. This comprehensive review presents the current knowledge about GABA transporters. Their distribution in the body, physiological functions and possible utilization in the therapy of different diseases were fully discussed. The important structural features were described based on published data, including sequence analysis, mutagenesis studies, and comparison with known SLC6 transporters for leucine (LeuT), dopamine (DAT) and serotonin (SERT). Moreover, the most important inhibitors of GABA transporters of various basic scaffolds, diverse selectivity and potency were presented.
γ-氨基丁酸（GABA）是神经系统中主要的抑制性神经递质。它在许多生理过程中发挥着关键作用。从突触前元件释放后，由于GABA转运体（GATs）的作用，它通过再摄取从突触间隙中被清除。GATs属于一个庞大的SLC6蛋白家族，其特征是神经递质通过细胞膜进行钠依赖性转运。GABA转运体在多种情况下都有特征描述，但它们的空间结构尚未完全清楚。它们分为四种类型，在分布和作用上有所不同。在此，特别关注了这些转运蛋白。这篇综述全面介绍了关于GABA转运体的现有知识。充分讨论了它们在体内的分布、生理功能以及在不同疾病治疗中的可能应用。基于已发表的数据描述了重要的结构特征，包括序列分析、诱变研究以及与已知的亮氨酸（LeuT）、多巴胺（DAT）和5-羟色胺（SERT）的SLC6转运体进行比较。此外，还介绍了各种基本骨架、不同选择性和效力的GABA转运体的最重要抑制剂。
