Glutamate

MDA MDA, mda, or ''variation'', may refer to: Places * Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics * Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...

receptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''GRIN2B''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

NMDA receptors

''N''-methyl-D-aspartate (

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

) receptors are a class of

ionotropic glutamate receptor Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in ...

s. The NMDA receptor channel has been shown to be involved in

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...

, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (

GRIN1 Glutamate MDAreceptor subunit zeta-1 is a protein that in humans is encoded by the ''GRIN1'' gene. The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily w ...

) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A ( GRIN2A), NMDAR2B (GRIN2B), NMDAR2C ( GRIN2C), and NMDAR2D ( GRIN2D). The NR2 subunit acts as the agonist binding site for

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.

Function

NR2B has been associated with age- and

visual The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (the ...

-experience-dependent plasticity in the

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...

of rats, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits. Both mice and rats that were engineered to over-express GRIN2B in their brains have increased mental ability. The "Doogie" mouse had double the learning ability on one measure of learning.

Ligands

Besonprodil Besonprodil (CI-1041) is a drug which acts as an NMDA antagonist, selective for the NR2B subunit. It is under development as a supplemental medication for Parkinson's disease, and has been shown in animals to be effective in counteracting the dys ...

CERC-301 Rislenemdaz (developmental code names CERC-301, MK-0657) is an orally-active, selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an adjunctive therapy for treatment-resistant depr ...

, a selective NR2B receptor antagonist *

Eliprodil Eliprodil (codenamed SL-82.0715) is an NMDA antagonist drug candidate which selectively inhibits the NR2B (GLUN2B) subtype NMDA receptor at submicromolar concentrations. Eliprodil failed a Phase III clinical trial for the treatment of acute ische ...

Ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

- apparent induction of dephosphorylation of the NR2B Tyr1472 residue by

STEP Step(s) or STEP may refer to: Common meanings * Stairs#Step, Steps, making a staircase * Walking * Dance move * Military step, or march ** Marching Arts Films and television * Steps (TV series), ''Steps'' (TV series), Hong Kong * Step (film), ' ...

, leading to reduced receptor function *

Ifenprodil Ifenprodil is an inhibitor of the NMDA receptor, specifically of GluN1 (glycine-binding NMDA receptor subunit 1) and GluN2B (glutamate-binding NMDA receptor subunit 2) subunits. Additionally, ifenprodil inhibits GIRK channels, and interacts with a ...

Rislenemdaz Rislenemdaz (developmental code names CERC-301, MK-0657) is an orally-active, selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an adjunctive therapy for treatment-resistant depre ...

* Evt 101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant. In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile. *

Felbamate Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associa ...

, an anticonvulsant that is also a

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

for the GABA_A receptor * Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist *

Traxoprodil Traxoprodil (developmental code name CP-101606) is a drug developed by Pfizer which acts as an NMDA antagonist, selective for the NR2B subunit. It has neuroprotective, analgesic, and anti-Parkinsonian effects in animal studies. Traxoprodil has ...

, a selective NR2B receptor antagonist *

Toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) at ...

- noncompetitive antagonist

Interactions

GRIN2B has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

Actinin, alpha 2 Alpha-actinin-2 is a protein which in humans is encoded by the ''ACTN2'' gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to ...

, *

DLG2 Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the ''DLG2'' gene. Function Chapsyn-110/PSD-93 a member of ...

, *

DLG3 Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the ''DLG3'' gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamil ...

, * DLG4, *

EXOC4 Exocyst complex component 4 is a protein that in humans is encoded by the ''EXOC4'' gene. Function The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to ...

, *

LIN7B Lin-7 homolog B is a protein that in humans is encoded by the ''LIN7B'' gene. Interactions LIN7B has been shown to interact with: * ACCN3, * GRIN2B, * KCNJ12 ATP-sensitive inward rectifier potassium channel 12 is a lipid-gated ion channel ...

, and *

RICS The Royal Institution of Chartered Surveyors (RICS) is a global professional body for surveyors, founded in London in 1868. It works at a cross-governmental level, and aims to promote and enforce the highest international standards in the val ...

NMDA receptors

Function

Ligands

Interactions

See also

References

Further reading