Gether Ulrik, Andersen Peter H, Larsson Orla M, Schousboe Arne
Molecular Neuropharmacology Group, Department of Pharmacology and Center for Pharmacogenomics, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Trends Pharmacol Sci. 2006 Jul;27(7):375-83. doi: 10.1016/j.tips.2006.05.003. Epub 2006 Jun 9.
The concentration of neurotransmitters in the extracellular space is tightly controlled by distinct classes of membrane transport proteins. This review focuses on the molecular function of two major classes of neurotransmitter transporter that are present in the cell membrane of neurons and/or glial cells: the solute carrier (SLC)1 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of glutamate, and the SLC6 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of dopamine, 5-HT, norepinephrine, glycine and GABA. Recent research has provided substantial insight into the structure and function of these transporters. In particular, the recent crystallizations of bacterial homologs are of the utmost importance, enabling the first reliable structural models of the mammalian neurotransmitter transporters to be generated. These models should be an important tool for developing specific drugs that, through selective interaction with transporters, could improve the treatment of serious neurological and psychiatric disorders.
细胞外空间中神经递质的浓度受到不同种类膜转运蛋白的严格控制。本综述聚焦于存在于神经元和/或神经胶质细胞膜中的两大类神经递质转运体的分子功能：溶质载体（SLC）1转运体家族，其包括介导谷氨酸钠依赖性摄取的转运体；以及SLC6转运体家族，其包括介导多巴胺、5-羟色胺、去甲肾上腺素、甘氨酸和γ-氨基丁酸钠依赖性摄取的转运体。最近的研究对这些转运体的结构和功能有了深入了解。特别是，细菌同源物的近期结晶至关重要，使得能够生成哺乳动物神经递质转运体的首个可靠结构模型。这些模型应成为开发特定药物的重要工具，这些药物通过与转运体的选择性相互作用，有望改善严重神经和精神疾病的治疗。
