Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: neurotoxic and therapeutic implications.
Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: neurotoxic and therapeutic implications.
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DOI：
10.1016/j.neuropharm.2008.07.002
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发表时间：
2009
影响因子：
4.7
通讯作者：
Hanson GR
中科院分区：
文献类型：
--
作者：
Fleckenstein AE;Volz TJ;Hanson GR
囊泡单胺转运蛋白-2 （VMAT-2）是神经元内单胺浓度和处置的重要调节剂，因为该蛋白隔离了关键的细胞质单胺能递质，并有助于它们随后的胞外释放。本文主要讨论精神活性药物（包括具有滥用潜力的药物）对多巴胺（DA）相关VMAT-2及其功能的影响。特别是，da相关的VMAT-2和相关囊泡对血浆摄取阻滞剂（如哌甲酯）和释放剂（如甲基苯丙胺）的不同反应。最近的临床前研究结果表明，泡状转运体系统是高度可调节的，既可以通过定位的改变，也可以通过VMAT-2蛋白动力学的改变。VMAT-2功能的这种变化表明存在可能影响DA系统活动的生理调节。此外，这些发现可能有助于我们了解药物滥用和帕金森病等多种da相关疾病的发病机制，并为治疗此类疾病提供新的治疗靶点。
The vesicular monoamine transporter-2 (VMAT-2) is an important regulator of intraneuronal monoamine concentrations and disposition as this protein sequesters critical cytoplasmic monoaminergic transmitters and contributes to their subsequent exocytotic release. This review primarily discusses the impact of psychoactive drugs (including those with abuse potential) on dopamine (DA)-related VMAT-2 and its function. In particular, the different responses by DA-related VMAT-2 and associated vesicles to plasmalemmal uptake blockers like methylphenidate and releasers like methamphetamine are presented. Recent preclinical findings suggest that vesicular transporter systems are highly regulatable, both by changes in localization as well as alterations in the kinetics of the VMAT-2 protein. The capacity for such shifts in VMAT-2 functions suggests the presence of physiological regulation that likely influences the activity of DA systems. In addition, these findings may contribute to our understanding of the pathogenesis of a variety of DA-related disorders such as substance abuse and Parkinson's disease and also suggest new therapeutic targets for treating such diseases.
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影响因子：
11.2
作者：
Frey, KA;Koeppe, RA;Kuhl, DE
通讯作者：
Kuhl, DE
影响因子：
4.7
作者：
Hogan, KA;Staal, RGW;Sonsalla, PK
通讯作者：
Sonsalla, PK
DOI：
10.1111/j.1600-0773.1999.tb00080.x
发表时间：
1999-09-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Kita, T;Takahashi, M;Nakashima, T
通讯作者：
Nakashima, T
影响因子：
4.7
作者：
Brown, JM;Hanson, GR;Fleckenstein, AE
通讯作者：
Fleckenstein, AE
影响因子：
3.4
作者：
Johanson, CE;Frey, KA;Schuster, CR
通讯作者：
Schuster, CR