脑儿茶酚胺稳态中的有机阳离子转运体。
Organic Cation Transporters in Brain Catecholamine Homeostasis.
机构信息
Department of Biomedical Sciences, Marquette University, Milwaukee, WI, USA.
出版信息
Handb Exp Pharmacol. 2021;266:187-197. doi: 10.1007/164_2021_470.
Catecholamines, including dopamine, norepinephrine, and epinephrine, are modulatory transmitters released from specialized neurons throughout the brain. Collectively, catecholamines exert powerful regulation of mood, motivation, arousal, and plasticity. Transporter-mediated uptake determines the peak concentration, duration, and physical spread of released catecholamines, thus playing key roles in determining the magnitude and duration of their modulatory effects. Most studies of catecholamine clearance have focused on the presynaptic high-affinity, low-capacity dopamine (DAT), and norepinephrine (NET) transporters, which are members of the uptake family of monoamine transporters. However, recent studies have demonstrated that members of the uptake family of monoamine transporters, including organic cation transporter 2 (OCT2), OCT3, and the plasma membrane monoamine transporter (PMAT) are expressed widely throughout the brain. In contrast to DAT and NET, these transporters have higher capacity and lower affinity for catecholamines and are multi-specific, each with the capacity to transport all catecholamines. The expression of these transporters in the brain suggests that they play significant roles in regulating catecholamine homeostasis. This review summarizes studies describing the anatomical distribution of OCT2, OCT3, and PMAT, their cellular and subcellular localization, and their contribution to the regulation of the clearance of catecholamines in the brain.
儿茶酚胺,包括多巴胺、去甲肾上腺素和肾上腺素,是从大脑中专门的神经元释放的调节性递质。儿茶酚胺共同对情绪、动机、觉醒和可塑性进行强有力的调节。转运体介导的摄取决定了释放的儿茶酚胺的峰值浓度、持续时间和物理扩散,从而在决定其调节作用的幅度和持续时间方面发挥关键作用。儿茶酚胺清除的大多数研究都集中在突触前高亲和力、低容量多巴胺(DAT)和去甲肾上腺素(NET)转运体上,它们是单胺转运体摄取家族的成员。然而,最近的研究表明,单胺转运体摄取家族的成员,包括有机阳离子转运体 2(OCT2)、OCT3 和质膜单胺转运体(PMAT),在大脑中广泛表达。与 DAT 和 NET 不同,这些转运体对儿茶酚胺的亲和力较低,但转运容量较高,且具有多特异性,每种转运体都能够转运所有的儿茶酚胺。这些转运体在大脑中的表达表明它们在调节儿茶酚胺稳态方面发挥着重要作用。本文综述了描述 OCT2、OCT3 和 PMAT 的解剖分布、细胞和亚细胞定位及其对脑内儿茶酚胺清除调节作用的研究。