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氨基胺诱导的多巴胺逆运输不需要细胞溶液Ca2

Jonatan Fullerton Støier¹, Ainoa Konomi-Pilkati¹, Mia Apuschkin¹

¹Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, Panum Institute - Maersk Tower 7.5, University of Copenhagen, Copenhagen, Denmark.

The Journal of biological chemistry

|July 19, 2023

概括

胺类药物 (AMPHs) 通过多巴胺转运体 (DAT) 引起多巴胺 (DA) 排放,而不会增加细胞内. 这种AMPH诱导的DA释放取决于囊泡单胺转运体-2和DAT活性.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
细胞生物学细胞生物学

背景情况:

氨基胺 (AMPHs) 是已知的多巴胺转运器 (DAT) 的基质,逆转多巴胺 (DA) 运输.
由AMPH诱导的DA排泄的确切机制,特别是它对细胞内的依赖,仍然不清楚.

研究的目的:

调查细胞质在AMPH诱导的DA流量中所扮演的角色,DA流量由内源性表达的DAT.中介.
在AMPH暴露期间同时可视化细胞外DA动态和细胞内Ca2+水平.

主要方法:

使用光传感器jRGECO1a (用于Ca2+) 和GRABDA1H (用于DA) 在培养的多巴胺基神经元和共培养的"嗅探器"细胞中.
通过四毒素阻断了外细胞DA释放,并评估了在DAT和膀单胺转运体-2抑制下AMPH诱导的DA流量.
使用通道阻断剂,化剂和NMDA受体激活操纵细胞内Ca2 +.

主要成果:

AMPH诱导了一种剂量依赖的DA流出,被DAT和囊泡单胺转运体-2抑制剂阻断.
这种流量与细胞溶液Ca2+的增加无关,并且不受通道阻塞或化影响.
激活NMDA受体增加了细胞质Ca2+而没有改变AMPH诱导的DA流动.
在D2受体阻塞时,AMPH触发了自发的Ca2+峰值,这表明了自受体依赖的Ca2+调节.

结论:

从多巴氨基神经元中AMPH诱导的DA流出独立于细胞质Ca2+.
排泄非常依赖AMPH对囊泡单胺转运体-2和DAT.的联合作用.
AMPH可能会通过D2自身受体调节细胞内Ca2+的作用,这与AMPH对DA流动的影响无关.

关键词:

氨基胺是一种安非他命.生物传感器生物传感器信号传递的.多巴胺运输体是多巴胺的运输体.基因编码的多巴胺传感器传感器现场光成像成像技术

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