Neurotransmitter transporters: molecular function of important drug targets.
The concentration of neurotransmitters in the extracellular space is tightly controlled by distinct classes of membrane transport proteins. This review focuses on the molecular function of two major classes of neurotransmitter transporter that are present in the cell membrane of neurons and/or glial cells: the solute carrier (SLC)1 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of glutamate, and the SLC6 transporter family, which includes the transporters that mediate the Na(+)-dependent uptake of dopamine, 5-HT, norepinephrine, glycine and GABA. Recent research has provided substantial insight into the structure and function of these transporters. In particular, the recent crystallizations of bacterial homologs are of the utmost importance, enabling the first reliable structural models of the mammalian neurotransmitter transporters to be generated. These models should be an important tool for developing specific drugs that, through selective interaction with transporters, could improve the treatment of serious neurological and psychiatric disorders.
Gether
Ulrik
U
Molecular Neuropharmacology Group, Department of Pharmacology and Center for Pharmacogenomics, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark. gether@neuropharm.ku.dk
Andersen
Peter H
PH
Larsson
Orla M
OM
Schousboe
Arne
A
D000818:Animals; D006801:Humans; D008958:Models, Molecular; D050479:Neurotransmitter Transport Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011955:Receptors, Drug / Q000187:drug effects*
D050479:Neurotransmitter Transport Proteins; D011955:Receptors, Drug