Gong Y, Zhang M, Cui L, Minuk G Y
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 2001 Dec;79(12):977-84.
Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a 32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.
γ-氨基丁酸（GABA）是哺乳动物大脑中主要的抑制性神经递质。尽管最初认为它仅限于中枢神经系统，但在全身的其他组织中也发现了GABA能活性。在本研究中，我们报告了人类GABA转运体cDNA的克隆和定位，并记录了其在各种人体组织中的表达情况。最初用32P标记的鼠脑GABA转运体3（GAT-3）cDNA探针筛选人肝cDNA文库，并通过使用Marathon-Ready人肾cDNA克隆全长cDNA。人类GABA转运体cDNA编码一个含有569个氨基酸的疏水蛋白，具有12个跨膜结构域（TMs）。对已发表序列的搜索显示，它与大鼠GAT-2、鼠GAT-3 cDNA、人类溶质载体家族6成员13（SLC6A13）以及一种人类外周甜菜碱/GABA转运体具有高度同源性。Northern印迹分析表明，人类GABA转运体在肾脏中强烈表达，在肝脏和大脑中的表达程度较低。该序列与人类12号染色体p13.3区域匹配良好，表明人类GABA转运体包含14个外显子。上述发现证实了人体组织中存在一种特定的GABA转运体，并对其进行了进一步的表征。
