Organic Cation Transporters in Brain Catecholamine Homeostasis

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 uptake₁ family of monoamine transporters. However, recent studies have demonstrated that members of the uptake₂ 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.