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 a nd blockers of uptake such as cocaine probably bind to both shared and separate domains on the transporter, which can be influenced dramatic ally by the presence of cations. Regulation of the dopamine transporte r occurs both by chronic occupancy with blocker and by acute effects o f D-2 dopamine receptors or second messengers such as diacylglycerol ( protein kinase C) and arachidonic acid. The dopamine transporter is in volved in the uptake of toxins generating Parkinson's disease; it is a lso an important target for psychostimulant drugs, ligands for in vivo imaging and medications used for neurologic diseases involving change s in the dopamine system. (C) 1997 Elsevier Science B.V.