Neurotransmitter transporters: molecular function of important drug targets

TY - JOUR

T1 - Neurotransmitter transporters

T2 - molecular function of important drug targets

AU - Gether, Ulrik

AU - Andersen, Peter H

AU - Larsson, Orla M

AU - Schousboe, Arne

PY - 2006/7

Y1 - 2006/7

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Models, Molecular

KW - Neurotransmitter Transport Proteins

KW - Protein Structure, Quaternary

KW - Protein Structure, Tertiary

KW - Receptors, Drug

U2 - 10.1016/j.tips.2006.05.003

DO - 10.1016/j.tips.2006.05.003

M3 - Journal article

C2 - 16762425

SN - 0165-6147

VL - 27

SP - 375

EP - 383

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

IS - 7

ER -