Pharmacology and regulation of the neuronal dopamine transporter

The dopamine transporter, a member of the family of Na+,Cl(-)-dependent transporters, mediates uptake of dopamine into dopaminergic neurons by an electrogenic, Na(+)- and Cl(-)-transport-coupled mechanism. Dopamine and blockers of uptake such as cocaine probably bind to both shared and separate domains on the transporter, which can be influenced dramatically by the presence of cations. Regulation of the dopamine transporter occurs both by chronic occupancy with blocker and by acute effects of D2 dopamine receptors or second messengers such as diacylglycerol (protein kinase C) and arachidonic acid. The dopamine transporter is involved in the uptake of toxins generating Parkinson's disease; it is also an important target for psychostimulant drugs, ligands for in vivo imaging and medications used for neurologic diseases involving changes in the dopamine system.