Meister B
Institutionen för histologi och neurobiologi, Karolinska institutet, Stockholm.
Lakartidningen. 1993 Mar 31;90(13):1255-9.
Neurotransmitter transporters terminate synaptic transmission by rapid sodium-dependent reaccumulation of released transmitter in the presynaptic nerve terminal. The transporters are major sites of action for psychostimulants such as amphetamine and cocaine, for antidepressants, and for neurotoxins that induce parkinsonism. The transporters for monoamines, choline, GABA (gamma-aminobutyric acid), glycine and glutamine have recently been cloned and characterised. Elucidation of the primary structures has shown that, with the exception of the glutamate transporter, the various proteins manifest substantial amino acid conservation and the presence of 12 putative transmembrane regions. The lack of homology with other proteins suggests these transporter proteins to represent a new gene family. Preliminary findings suggest the distribution of neurotransmitter gene expression to match that of presynaptic markers of the respective transmitter systems, though in some areas the distribution of transporter mRNA expression has been found to be uneven. There is evidence suggesting neurotransmitter transporters to be involved in the pathophysiology of certain neurodegenerative diseases, and there are indications that drugs affecting transporter proteins may assume increasing clinical importance.
神经递质转运体通过在突触前神经末梢中快速依赖钠的方式重新积累释放的递质来终止突触传递。这些转运体是苯丙胺和可卡因等精神兴奋剂、抗抑郁药以及诱发帕金森症的神经毒素的主要作用位点。单胺、胆碱、GABA(γ-氨基丁酸)、甘氨酸和谷氨酰胺的转运体最近已被克隆和鉴定。一级结构的阐明表明,除了谷氨酸转运体之外,各种蛋白质表现出大量的氨基酸保守性以及12个假定的跨膜区域。与其他蛋白质缺乏同源性表明这些转运体蛋白代表一个新的基因家族。初步研究结果表明,神经递质基因表达的分布与各自递质系统的突触前标记物的分布相匹配,不过在某些区域已发现转运体mRNA表达的分布并不均匀。有证据表明神经递质转运体参与某些神经退行性疾病的病理生理过程,并且有迹象表明影响转运体蛋白的药物可能在临床上变得越来越重要。