Glycine transporter

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Glycine transporters (GlyTs) are plasmalemmal neurotransmitter transporters. They serve to terminate the signaling of glycine by mediating its reuptake from the synaptic cleft back into the presynaptic neurons. There are two glycine transporters: glycine transporter 1 (GlyT1) and glycine transporter 2 (GlyT2). [1]

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.

Glycine chemical compound

Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest amino acid, with the chemical formula NH2CH2‐COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is also known as a "helix breaker", due to its ability to act as a hinge in the secondary structure of proteins.

Reuptake

Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse.

See also

GABA transporters (Gamma-Aminobutyric acid transporters) belong to the family of neurotransmitters known as sodium symporters, also known as solute carrier 6 (SLC6). These are large family of neurotransmitter which are Na+ concentration dependent. They are found in various regions of the brain in different cell types, such as neurons and astrocytes. These transporters are primarily responsible for the regulation of extracellular GABA concentration during basal and synaptic activity. They are responsible to create a GABA gradient which is determined by the membrane potential, and the concentration of Na+ and Cl-. They are also present on the plasma membrane of neurons and glia which help define their function of regulation of GABA concentration as they act as the receptors that facilitate recycling of GABA in the extracellular space. GABA transporters often are the main sites that are aimed by lot of anticonvulsant drugs in order to avoid seizure disorders such as epilepsy.

Glycine receptor

The glycine receptor is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.

A glycine reuptake inhibitor (GRI) is a type of drug which inhibits the reuptake of the neurotransmitter glycine by blocking one or more of the glycine transporters (GlyTs). Examples of GRIs include bitopertin (RG1678), Org 24598, Org 25935, ALX-5407, and sarcosine, which are selective GlyT1 blockers, and Org 25543 and N-arachidonylglycine, which are selective GlyT2 blockers. Some weak and/or non-selective GlyT blockers include amoxapine and ethanol (alcohol).

Related Research Articles

Serotonin–norepinephrine reuptake inhibitor class of antidepressant drugs used in the treatment of major depressive disorder

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs that treat major depressive disorder (MDD) and can also treat anxiety disorders, obsessive–compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

Norepinephrine transporter protein-coding gene in the species Homo sapiens

The norepinephrine transporter (NET), also known as solute carrier family 6 member 2 (SLC6A2), is a protein that in humans is encoded by the SLC6A2 gene.

Serotonin reuptake inhibitor

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

A neurotransmitter sodium symporter (NSS) (TC# 2.A.22) is type of neurotransmitter transporter that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na+ symport mechanism. The NSS family is a member of the APC superfamily. Its constituents have been found in bacteria, archaea and eukaryotes.

Glycine transporter 2 protein-coding gene in the species Homo sapiens

Glycine transporter 2 (GlyT2) also known as the sodium- and chloride-dependent glycine transporter 2 or solute carrier family 6 member 5 is a protein that in humans is encoded by the SLC6A5 gene.

Glycine transporter 1 protein-coding gene in the species Homo sapiens

Sodium- and chloride-dependent glycine transporter 1 is a protein that in humans is encoded by the SLC6A9 gene.

Reuptake inhibitor

A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.

Norepinephrine–dopamine reuptake inhibitor

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.

Reuptake enhancer

A reuptake enhancer (RE), also sometimes referred to as a reuptake activator, is a type of reuptake modulator which enhances the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to a decrease in the extracellular concentrations of the neurotransmitter and therefore a decrease in neurotransmission.

ORG-25935 chemical compound

ORG-25935, also known as SCH-900435 is a synthetic drug developed by Organon International, which acts as a selective inhibitor of the glycine transporter GlyT-1. In animal tests it reduces alcohol consumption and has analgesic and anticonvulsant effects, but it has mainly been studied for its antipsychotic properties, and in human trials it was shown to effectively counteract the effects of the dissociative drug ketamine.

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

Bitopertin chemical compound

Bitopertin is a glycine reuptake inhibitor which was under development by Roche as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally-controlled positive symptoms associated with schizophrenia. Research into this indication has been largely halted as a result of disappointing trial results, but Roche continues to develop bitopertin for the treatment of obsessive-compulsive disorder (OCD).

An excitatory amino acid reuptake inhibitor (EAARI) is a type of drug which inhibits the reuptake of the excitatory neurotransmitters glutamate and aspartate by blocking one or more of the excitatory amino acid transporters (EAATs).

Bacterial Leucine Transporter

Bacterial Leucine Transporter (LeuT) is a bundled twelve alpha helix protein which belongs to the family of transporters that shuttle amino acids in and out of bacterial cells. Specialized in small hydrophobic amino acids such as leucine and alanine, this transporter is powered by the gradient of sodium ions that is normally maintained by healthy cells across their membranes. LeuT acts as a symporter, which means that it links the passage of a sodium ion across the cell membrane with the transport of the amino acid in the same direction. It was first crystallized to understand the inner molecular mechanisms of antidepressant's work since it has a close resemblance with the human neurotransmitter transporters that these drugs block, thus inhibiting the reuptake of chemical messengers across the cell membrane of nerve axons and glial cells.

An amino acid reuptake inhibitor (AARI) is a type of drug which inhibits the reuptake of one or more amino acid neurotransmitters by blocking one or more of their respective transporters. They include excitatory amino acid reuptake inhibitors, GABA reuptake inhibitors, and glycine reuptake inhibitors.

BIIB-104

BIIB-104, also known as PF-04958242 is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which is under development by Pfizer for the treatment of cognitive symptoms in schizophrenia. It was also under development for the treatment of age-related sensorineural hearing loss, but development for this indication was terminated due to insufficient effectiveness. As of July 2018, BIIB-104 is in phase II clinical trials for cognitive symptoms in schizophrenia.

References

  1. Harvey RJ, Yee BK (November 2013). "Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain". Nat Rev Drug Discov. 12 (11): 866–85. doi:10.1038/nrd3893. PMID   24172334.