Neurotransmitter transporter

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.^[1]

Vesicular transporters move neurotransmitters into synaptic vesicles, regulating the concentrations of substances within them.^[2] Vesicular transporters rely on a proton gradient created by the hydrolysis of adenosine triphosphate (ATP) in order to carry out their work: vesicle ATPase hydrolyzes ATP, causing protons to be pumped into the Synaptic vesicles and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle.^[3]

Neurotransmitter transporters frequently use electrochemical gradients that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by the cotransport, or symport, of Na⁺ in order to move glutamate across membranes.

Normally, transporters in the synaptic membrane serve to remove neurotransmitters from the synaptic cleft and prevent their action or bring it to an end. However, on occasion transporters can work in reverse, transporting neurotransmitters into the synapse, allowing these neurotransmitters to bind to their receptors and exert their effect. This "nonvesicular release" of neurotransmitters is used by some cells, such as amacrine cells in the retina, as a normal form of neurotransmitter release.^[4]

Types

Specific types of neurotransmitter transporters include the following:

• Glutamate/aspartate transporters, including:
  • Excitatory amino acid transporter 1 (EAAT1)
  • Excitatory amino acid transporter 2 (EAAT2)
  • Excitatory amino acid transporter 3 (EAAT3)
  • Excitatory amino acid transporter 4 (EAAT4)
  • Excitatory amino acid transporter 5 (EAAT5)
  • Vesicular glutamate transporter 1 (VGLUT1)
  • Vesicular glutamate transporter 2 (VGLUT2)
  • Vesicular glutamate transporter 3 (VGLUT3)

• GABA transporters, including:
  • GABA transporter type 1 (GAT1)
  • GABA transporter type 2 (GAT2)
  • GABA transporter type 3 (GAT3)
  • Betaine transporter (BGT1)
  • Vesicular GABA transporter (VGAT)

• Glycine transporters, including:
  • Glycine transporter type 1 (GlyT1)
  • Glycine transporter type 2 (GlyT2)

• Monoamine transporters, including:
  • Dopamine transporter (DAT)
  • Norepinephrine transporter (NET)
  • Serotonin transporter (SERT)
  • Vesicular monoamine transporter 1 (VMAT1)
  • Vesicular monoamine transporter 2 (VMAT2)

• Adenosine transporters, including:
  • Equilibrative nucleoside transporter 1 (ENT1)
  • Equilibrative nucleoside transporter 2 (ENT2)
  • Equilibrative nucleoside transporter 3 (ENT3)
  • Equilibrative nucleoside transporter 4 (ENT4)

• Vesicular acetylcholine transporter (VAChT)^[5]

Note that there is no plasmalemmal acetylcholine transporter, as acetylcholine is terminated via rapid metabolism into choline by cholinesterase enzymes, and choline is subsequently transported back into the cell and reconverted into acetylcholine.

Transporters associated with histamine and the endocannabinoids have not yet been identified.

Clinical significance

Antidepressants such as SSRIs, SNRIs and TCAs suppress the activity of serotonin and/or norepinephrine transporters, preventing the reuptake of targeted neurotransmitters from the synaptic cleft.

Psychostimulants like cocaine, amphetamines, and methylphenidate act by inhibiting and/or reversing the dopamine and norepinephrine transporters. Some dissociatives like phencyclidine and ketamine are also dopamine transporter blockers.

Tiagabine, a drug used as an anticonvulsant, acts by inhibiting the GABA transporter 1.

References

1. ^ Iversen L (July 2000). "Neurotransmitter transporters: fruitful targets for CNS drug discovery". Mol. Psychiatry 5 (4): 357–62. doi:10.1038/sj.mp.4000728. PMID 10889545. http://www.biopsychiatry.com/transporters.htm. 
2. ^ Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, Copenhagen DR (January 2003). "Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate". J. Neurosci. 23 (2): 518–29. PMID 12533612. http://www.jneurosci.org/cgi/content/full/23/2/518. 
3. ^ Kandel ER, Schwartz JH, Jessell TM (2000). Principles of neural science (4th ed.). New York: McGraw-Hill. p. 287. ISBN 0-8385-7701-6. 
4. ^ Kandel ER, Schwartz JH, Jessell TM (2000). Principles of neural science (4th ed.). New York: McGraw-Hill. p. 295. ISBN 0-8385-7701-6. 
5. ^ Weihe E, Tao-Cheng JH, Schäfer MK, Erickson JD, Eiden LE (April 1996). "Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles". Proc Natl Acad Sci USA. 93 (8): 3547–52. doi:10.1073/pnas.93.8.3547. PMC 39647. PMID 8622973. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8622973. 

External links

• MeSH Neurotransmitter+Transporters
• Clearing Your Mind of Neurotransmitters: Functional Impact of Neurotransmitter Transporter Gene Variants - a videocast of the lecture by Randy Blakely, Ph.D., Vanderbilt University. Part of NIH Neuroscience Seminar series. 450 Mb file, .m4v format.
• The Blakely Lab - Laboratory exploring the molecular basis for neurotransmitter transporter structure, function and regulation.

This anatomy article is a stub. You can help Wikipedia by expanding it.v · Categories: Neurotransmitter transporters Integral membrane proteins Anatomy stubs Wikimedia Foundation. 2010. Игры ⚽ Нужен реферат? Reach Township, Ontario Balarampur, Budgebudge Look at other dictionaries: Transporter Classification database — (or TCDB) is an IUBMB approved classification system for membrane transport proteins including ion channels. This classification system was designed to be analogous to the EC number system for classifying enzymes, but it also uses phylogenetic… …   Wikipedia Neurotransmitter uptake inhibitor — A neurotransmitter uptake inhibitor is a drug which inhibits the reuptake of the neurotransmitter, thus extending the duration of its effect.Examples include: * Adrenergic uptake inhibitor/Norepinephrine reuptake inhibitor * Dopamine reuptake… …   Wikipedia Norepinephrine transporter — Solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 Identifiers Symbols SLC6A2; NAT1; NET; NET1; SLC6A5 External IDs …   Wikipedia Dopamine transporter — Solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 Identifiers Symbols …   Wikipedia Serotonin transporter — The serotonin transporter (SERT) is a monoamine transporter protein. This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the… …   Wikipedia Glutamate transporter — Glutamate transporters, also known as VGLUT, are neurotransmitter transporters that exist in the membranes of neurons and glial cells to remove excess amounts of the neurotransmitters glutamate and aspartate from the synapse. Glutamate is the… …   Wikipedia SLC-Transporter — ist ein Sammelbegriff für etwa 48 Familien von menschlichen Transportproteinen (so genannte Carrier oder Membranproteine) mit bald 400 Genen. Solute, die transportiert werden, können geladene und ungeladene organische Moleküle, sowie anorganische …   Deutsch Wikipedia Ion transporter — Ion pump redirects here. For pumps that reduce pressure, see Ion pump (physics). In biology, an ion transporter, also called an ion pump, is a transmembrane protein that moves ions across a plasma membrane against their concentration gradient, in …   Wikipedia Vesicular acetylcholine transporter — protein Name=solute carrier family 18 (vesicular acetylcholine), member 3 caption= width= HGNCid=10936 Symbol=SLC18A3 AltSymbols= EntrezGene=6572 OMIM=600336 RefSeq=NM 003055 UniProt=Q16572 PDB= ECnumber= Chromosome=10 Arm=q Band=11.2… …   Wikipedia Monoamine transporter — Dopamine Transporter (DAT 6) Monoamine transporters (MATs) are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT,… …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”