Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications
Organic Cation Transporters in Brain Histamine Clearance: Physiological and Psychiatric Implications
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脑组胺清除中的有机阳离子转运蛋白：生理和精神影响
DOI：
10.1007/164_2021_447
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发表时间：
2021
影响因子：
--
通讯作者：
Yoshikawa Takeo
中科院分区：
文献类型：
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作者：
Naganuma Fumito;Yoshikawa Takeo
组胺是中枢神经系统中的一种神经递质，参与多种生理功能。最近的研究已经确定了组胺能系统减少在各种神经疾病中的致病作用。因此，脑组胺系统作为改善脑功能的治疗靶点而备受关注。神经递质清除是调节神经元活动的最重要的过程之一，也是多种药物的重要靶点。我们以前的研究已经证明了组胺N-甲基转移酶对组胺失活的重要性以及该酶在细胞内的定位；研究表明，将带正电的组胺从细胞外转移到细胞内的运输系统是组胺失活的先决条件。一些关于体外星形细胞组胺转运的研究表明，有机阳离子转运体3(Oct3)和质膜单胺转运体(PmAt)在组胺摄取中起作用，但这些转运体在体内组胺清除中的重要性尚不清楚。免疫组织化学分析显示Oct3和pmAt在神经元上的表达，强调了研究神经元组胺摄取的重要性。利用基因敲除小鼠或快速扫描循环伏安法进行的进一步研究将加速组胺转运体的研究。在这篇综述文章中，我们总结了组胺转运试验，并描述了负责组胺在大脑中转运的候选转运体。
Histamine acts as a neurotransmitter in the central nervous system and is involved in numerous physiological functions. Recent studies have identified the causative role of decreased histaminergic systems in various neurological disorders. Thus, the brain histamine system has attracted attention as a therapeutic target to improve brain function. Neurotransmitter clearance is one of the most important processes for the regulation of neuronal activity and is an essential target for diverse drugs. Our previous study has shown the importance of histamineN-methyltransferase for the inactivation of brain histamine and the intracellular localization of this enzyme; the study indicated that the transport system for the movement of positively charged histamine from the extracellular to intracellular space is a prerequisite for histamine inactivation. Several studies on in vitro astrocytic histamine transport have indicated the contribution of organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) in histamine uptake, although the importance of these transporters in in vivo histamine clearance remains unknown. Immunohistochemical analyses have revealed the expression of OCT3 and PMAT on neurons, emphasizing the importance of investigating neuronal histamine uptake. Further studies using knockout mice or fast-scan cyclic voltammetry will accelerate the research on histamine transporters. In this review article, we summarize histamine transport assays and describe the candidate transporters responsible for histamine transport in the brain.