INSERM U1130, Paris F-75005, France; CNRS UMR 8246, Paris F-75005, France; Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France; Université Paris Descartes, Ecole Doctorale Médicament Toxicologie Chimie Environnement, Paris F-75006, France.
INSERM U1130, Paris F-75005, France; CNRS UMR 8246, Paris F-75005, France; Sorbonne Universités, UPMC Univ Paris 06, Paris F-75005, France.
Pharmacol Ther. 2015 Feb;146:94-103. doi: 10.1016/j.pharmthera.2014.09.008. Epub 2014 Sep 22.
Organic cation transporters (OCTs) are polyspecific facilitated diffusion transporters that contribute to the absorption and clearance of various physiological compounds and xenobiotics in mammals, by mediating their vectorial transport in kidney, liver or placenta cells. Unexpectedly, a corpus of studies within the last decade has revealed that these transporters also fulfill important functions within the brain. The high-affinity monoamine reuptake transporters (SERT, NET and DAT) exert a crucial role in the control of aminergic transmission by ensuring the rapid clearance of the released transmitters from the synaptic cleft and their recycling into the nerve endings. Substantiated evidence indicate that OCTs may serve in the brain as a compensatory clearance system in case of monoamine spillover after high-affinity transporter blockade by antidepressants or psychostimulants, and in areas of lower high-affinity transporter density at distance from the aminergic varicosities. In spite of similar anatomical profiles, the two brain OCTs, OCT2 and OCT3, show subtle differences in their distribution in the brain and their functional properties. These transporters contribute to shape a variety of central functions related to mood such as anxiety, response to stress and antidepressant efficacy, but are also implicated in other processes like osmoregulation and neurotoxicity. In this review, we discuss the recent knowledge and emerging concepts on the role of OCTs in the uptake of aminergic neurotransmitters in the brain and in these various physiological functions, focusing on the implications for mental health.
有机阳离子转运体（OCTs）是多特异性促进扩散转运体，通过介导肾脏、肝脏或胎盘细胞中各种生理化合物和外源性化学物质的载体转运，促进其吸收和清除。出乎意料的是，过去十年中的一系列研究揭示了这些转运体在大脑中也具有重要功能。高亲和力单胺类再摄取转运体（SERT、NET 和 DAT）通过确保从突触间隙快速清除释放的递质并将其回收至神经末梢，从而在控制胺能传递中发挥关键作用。有充分证据表明，在高亲和力转运体被抗抑郁药或精神兴奋剂阻断后，单胺溢出时，OCTs 可能在大脑中作为一种代偿性清除系统发挥作用，并且在远离胺能末梢的低亲和力转运体密度区域发挥作用。尽管具有相似的解剖学特征，但两种脑 OCT 转运体 OCT2 和 OCT3 在大脑中的分布和功能特性上存在细微差异。这些转运体有助于形成与情绪相关的多种中枢功能，如焦虑、应激反应和抗抑郁疗效，但也与其他过程有关，如渗透压调节和神经毒性。在这篇综述中，我们讨论了 OCTs 在脑内摄取胺能神经递质以及在这些各种生理功能中的作用的最新知识和新兴概念，重点讨论了其对心理健康的影响。
