Pathways & interactions
Sodium:neurotransmitter symporter, dopamine (IPR002436)
Short name: Na/ntran_symport_dopamine
- Sodium:neurotransmitter symporter (IPR000175)
- Sodium:neurotransmitter symporter, dopamine (IPR002436)
Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions [PMID: 15336049]. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na+ and Cl-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na+ and the counter-transport of K+, with no apparent dependence on Cl- [PMID: 8811182]. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [PMID: 8103691, PMID: 7823024].
Sequence analysis of the Na+/Cl- neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters [PMID: 9779464].
In the mammalian brain, the dopamine system is thought to be involved in the control of locomotion, cognition and endocrine function. The dopamine transporter is critical for the removal of dopamine from the extracellular space, following its release, and is the principal site of action for psycho-stimulant drugs, such as cocaine and amphetamines, which inhibit the transporter's activity. A single form of dopamine transporter (containing ~620 amino acids) has been isolated from humans and other mammals. Studies of its brain distribution show transcripts to be present in areas previously established to possess dopaminergic systems, such as the substantia nigra and ventral tegmental area, which regions are known to contain dopaminergic cell bodies [PMID: 1406597]. Targeted gene disruption of the dopamine transporter has confirmed its importance in maintaining low extracellular dopamine levels. Mice lacking the transporter show profound alterations in the homeostasis of the nigrostriatal dopamine system of the brain. Extracellular levels of dopamine are elevated and removal of released dopamine is ~300 times slower then in control mice. Additionally, the rather stereotyped behavioural responses observed in response to administration of cocaine or amphetamine are greatly attenuated [PMID: 10435196].
- PR01202 (DOPTRANSPORT)