Structure and function
of the dopamine transporter

by
Chen N, Reith ME
Department of Biomedical and Therapeutic Sciences,
College of Medicine,
University of Illinois,
Box 1649, 61656,
Peoria, IL, USA
Eur J Pharmacol 2000 Sep 29; 405(1-3):329-339


ABSTRACT

The dopamine transporter mediates uptake of dopamine into neurons and is a major target for various pharmacologically active drugs and environmental toxins. Since its cloning, much information has been obtained regarding its structure and function. Binding domains for dopamine and various blocking drugs including cocaine are likely formed by interactions with multiple amino acid residues, some of which are separate in the primary structure but lie close together in the still unknown tertiary structure. Chimera and site-directed mutagenesis studies suggest the involvement of both overlapping and separate domains in the interaction with substrates and blockers, whereas recent findings with sulfhydryl reagents selectively targeting cysteine residues support a role for conformational changes in the binding of blockers such as cocaine. The dopamine transporter can also operate in reverse, i.e. in an efflux mode, and recent mutagenesis experiments show different structural requirements for inward and outward transport. Strong evidence for dopamine transporter domains selectively influencing binding of dopamine or cocaine analogs has not yet emerged, although the development of a cocaine antagonist at the level of the transporter remains a possibility.
D1
RDS
Recovery
Dopamine
Amineptine
Methylphenidate
Tranylcypromine
Drugs and reward
The pleasure and the pain
The dopamine transporter
Reward deficiency syndrome
Dopamine and reward-signalling
Dopamine deficiency and depression
Dopamine transporters and depression
Pain, motivation, pleasure and the rostral shell
Depression, dopamine and dextroamphetamine
Mesolimbic medium spiny neurons and pleasure
Regulation of synapses in the nucleus accumbens
Opioids for pleasure and dopamine for anticipation?
The nucleus accumbens: opioids versus cannabinoids
Greater availability of dopamine transporters in depression


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