Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry.
Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry.
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DOI：
10.1002/med.20187
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发表时间：
2011-07
影响因子：
13.3
通讯作者：
Wimalasena, Kandatege
中科院分区：
文献类型：
--
作者：
Wimalasena, Kandatege
关键词：
囊泡单胺转运体（VMAT）负责单胺能神经元将胞质单胺摄取到突触囊泡中。两个密切相关的VMAT具有不同的药理学特性和组织分布的特点。VMAT 1优先在神经内分泌细胞中表达，VMAT 2主要在CNS中表达。各种精神兴奋剂的神经毒性和成瘾特性至少部分归因于它们对VMAT2功能的干扰。通过PET扫描对VMAT 2密度的定量评估在临床上可用于早期诊断和监测帕金森病和阿尔茨海默病以及药物成瘾的进展。经典的VMAT 2抑制剂丁苯那嗪长期以来在英国、加拿大和澳大利亚用于治疗与亨廷顿病相关的舞蹈病，最近在美国获得批准。VMAT2成像也可用于利用糖尿病的发作，因为VMAT2也在胰腺的β细胞中表达。VMAT1基因SLC18A1是一个与精神分裂症连锁的位点，因此，VMAT1基因的多态性形式可能赋予精神分裂症的易感性。本文综述了目前对VMAT 2结构与功能关系的了解、VMAT 2在成瘾和精神兴奋剂诱导的神经毒性中的作用以及特定VMAT 2配体的治疗和诊断应用。本文还讨论了VMAT 1基因与精神分裂症和双相情感障碍I的连锁证据。
Vesicular monoamine transporters (VMAT) are responsible for the uptake of cytosolic monoamines into synaptic vesicles in monoaminergic neurons. Two closely related VMATs with distinct pharmacological properties and tissue distributions have been characterized. VMAT1 is preferentially expressed in neuroendocrine cells and VMAT2 is primarily expressed in the CNS. The neurotoxicity and addictive properties of various psychostimulants have been attributed, at least partly, to their interference with VMAT2 functions. The quantitative assessment of the VMAT2 density by PET scanning has been clinically useful for early diagnosis and monitoring of the progression of Parkinson’s and Alzheimer’s diseases and drug addiction. The classical VMAT2 inhibitor tetrabenazine has long been used for the treatment of chorea associated with Huntington’s disease in UK, Canada and Australia and recently approved in the US. The VMAT2 imaging may also be useful for exploiting the onset of diabetes mellitus, since VMAT2 is also expressed in the β-cells of the pancreas. VMAT1 gene SLC18A1 is a locus with strong evidence of linkage with schizophrenia and thus, the polymorphic forms of the VMAT1 gene may confer susceptibility to schizophrenia. This review summarizes the current understanding of the structure-function relationships of VMAT2, and the role of VMAT2 on addiction and psychostimulant induced neurotoxicity, and the therapeutic and diagnostic applications of specific VMAT2 ligands. The evidence for the linkage of VMAT1 gene with schizophrenia and bipolar disorder I are also discussed.
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影响因子：
6.1
作者：
DASILVA, JN;KILBOURN, MR
通讯作者：
KILBOURN, MR
影响因子：
4.5
作者：
Eiden, LE;Schäfer, MKH;Schütz, B
通讯作者：
Schütz, B
DOI：
10.1002/jlcr.2580330413
发表时间：
1993-04-01
影响因子：
1.8
作者：
CANNEY, DJ;GUO, YZ;KUNG, HF
通讯作者：
KUNG, HF
影响因子：
--
作者：
DALBY, MA
通讯作者：
DALBY, MA
影响因子：
3.1
作者：
DASILVA, JN;CAREY, JE;KILBOURN, MR
通讯作者：
KILBOURN, MR