Regulation of the ability of a neurotransmitter [our focus: serotonin, norepinephrine, dopamine, acetylcholine, glycine, and gamma-aminobutyric acid (GABA)] to reach its receptor targets is regulated in part by controlling the access the neurotransmitter has to receptors. Transporters, located at both the cellular plasma membrane and in subcellular vesicles, carry a myriad of responsibilities that include enabling neurotransmitter release and controlling uptake of neurotransmitter back into a cell or vesicle. Driven largely by electrochemical gradients, these transporters move neurotransmitters. The regulation of the transporters themselves through changes in expression and/or posttranslational modification allows for fine-tuning of this system. Transporters have been best recognized as targets for psychoactive stimulants and remain a mainstay target of primarily central nervous system (CNS) acting drugs for treatment of debilitating diseases such as depression and anxiety. Studies reveal, however, that transporters are found and functional in tissues outside the CNS (gastrointestinal and cardiovascular tissues, for example). The importance of neurotransmitter transporters is underscored with discoveries that dysfunction of transporters can cause life-changing disease. This article provides a high-level review of major classes of both plasma membrane transporters and vesicular transporters. © 2021 American Physiological Society. Compr Physiol 11:2279-2295, 2021.
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