glycine receptor α2 subunit | Glycine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

glycine receptor α2 subunit

Target id: 424

Nomenclature: glycine receptor α2 subunit

Family: Glycine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for glycine receptor α2 subunit in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 452 Xp22.1-p21.3 GLRA2 glycine receptor alpha 2 3
Mouse 4 452 X F5 Glra2 glycine receptor, alpha 2 subunit 8
Rat 4 452 Xq21 Glra2 glycine receptor, alpha 2 5
Previous and Unofficial Names
GLR | Glycine receptor alpha 2 subunit (glycine receptor neonatal) | glycine receptor strychnine-binding subunit | RNNEOGLY | glycine receptor, alpha 2 | glycine receptor
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
γ = 111 pS (main state); (+ β = 54 pS)
Natural/Endogenous Ligands
glycine
Selective agonists (potency order) (Human)
glycine > β-alanine > taurine

Download all structure-activity data for this target as a CSV file

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
pregnenolone sulphate Hs Antagonist 5.3 pKi
pKi 5.3 (Ki 5.5x10-6 M)
tropisetron Hs Antagonist 4.9 pKi
pKi 4.9 (Ki 1.3x10-5 M)
HU-210 Hs Antagonist 7.0 pIC50
pIC50 7.0 (IC50 9x10-8 M)
WIN55212-2 Hs Antagonist 6.7 pIC50
pIC50 6.7 (IC50 2.2x10-7 M)
HU-308 Hs Antagonist 6.0 pIC50
pIC50 6.0 (IC50 1.1x10-6 M)
ginkgolide X Hs Antagonist 5.6 pIC50
pIC50 5.6 (IC50 2.8x10-6 M)
bilobalide Hs Antagonist 5.1 pIC50
pIC50 5.1 (IC50 8x10-6 M)
colchicine Hs Antagonist 4.2 pIC50
pIC50 4.2 (IC50 6.4x10-5 M)
5,7-dichlorokynurenic acid Hs Antagonist 3.7 pIC50
pIC50 3.7 (IC50 1.88x10-4 M)
strychnine Hs Antagonist - -
[3H]strychnine Hs Antagonist - -
PMBA Hs Antagonist - -
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
picrotoxinin Hs - no 6.4 pIC50 - no
pIC50 6.4 (IC50 4.1x10-7 M)
Not voltage dependent
picrotoxin Hs - no 5.6 pIC50 - no
pIC50 5.6 (IC50 2.3x10-6 M)
Not voltage dependent
ginkgolide B Hs - no 4.9 – 5.4 pIC50 - no
pIC50 4.9 – 5.4 (IC50 1.14x10-5 – 3.7x10-6 M)
Not voltage dependent
picrotin Hs - no 4.9 pIC50 - no
pIC50 4.9 (IC50 1.31x10-5 M)
Not voltage dependent
cyanotriphenylborate Hs - no >4.7 pIC50 - no 11
pIC50 >4.7 (IC50 <2x10-5 M) [11]
Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
Zn2+ Hs Potentiation 6.3 pEC50 - no
pEC50 6.3 (EC50 5.4x10-7 M) endogenous; not affected by β subunit co-expression
Not voltage dependent
Δ9-tetrahydrocannabinol Hs Potentiation ~6.0 pEC50 - no
pEC50 ~6.0 (EC50 ~1x10-6 M) ~230% potentiation
Not voltage dependent
Cu2+ Hs Inhibition 4.8 pIC50 - no
pIC50 4.8 (IC50 1.7x10-5 M) endogenous
Not voltage dependent
Zn2+ Hs Inhibition 3.4 pIC50 - no
pIC50 3.4 (IC50 3.6x10-4 M) endogenous
Not voltage dependent
Tissue Distribution
Retina (bipolar cells, amacrine cells and some ganglion cells in inner plexiform layer)
Species:  Mouse
Technique:  Immunocytochemistry
References:  4
Tenia tecta, piriform cortex, infralimbic cortex, layer VI cerebral cortex, hippocampus (CA1, CA2, CA4 and dentate gyrus), geniculate and supergeniculate nuclei, dorsal horn of spinal cord
Species:  Rat
Technique:  In situ hybridisation
References:  7
Retina (amacrine cells in inner half of the inner nuclear layer and nearly all cells in the ganglion cell layer)
Species:  Rat
Technique:  In situ hybridisation
References:  2
Neutrophils and macrophages
Species:  Rat
Technique:  RT-PCR
References:  1
Neural stem progenitor cells
Species:  Rat
Technique:  RT-PCR
References:  10
Gene Expression and Pathophysiology
GlyR α2 knockout mice
Tissue or cell type:  embryonic stem cells
Pathophysiology:  Knock out mice displayed no overt behavioural phenotype or neuroanatomical changes. In particular they did not exhibit startle symptoms. However, cortical neurons were no longer responsive to applied glycine.
Species:  Mouse
Technique:  gene targeting ' gene knockout' in embryonic stem cells, whole cell patch-clamp electrophysiology
References:  13
Targeted knockdown of α2 GlyR
Tissue or cell type:  embryonic cells
Pathophysiology:  Targeted knockdown of α2 GlyR decreased the number of photoreceptors while increasing the number of other retinal cell types.
Species:  Mouse
Technique:  siRNA interference
References:  12
Gain-of-function experiments to increase expression of α2
Tissue or cell type:  embryonic cells
Pathophysiology:  Enhanced α2 GlyR expression induced exit from mitosis, and results in an increase in rod photoreceptor numbers
Species:  Mouse
Technique:  retroviral mediated gene transfer
References:  12
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  GlyR α2A and α2B splice variants differ by an adjacent dual amino acid substitution in the N-terminal domain (V58I, T59A). The α2B subunit exhibited significantly higher glycine sensitivity and is expressed at higher levels in the adult rat.
References:  5,9
Type:  Splice variant
Species:  Rat
Description:  The GlyR α2N splice variant lacks exon 3 and hence is not expressed.
References:  6
General Comments
The rat glycine receptor α2 subunit exists as two splice variants (α2A and α2B) that differ by a dual, adjacent amino acid substitution from α2A(V58,T59) to α2B(I58,A59) in the N-terminal extracellular domain [5].

References

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1. Froh M, Thurman RG, Wheeler MD. (2002) Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes. Am. J. Physiol. Gastrointest. Liver Physiol., 283 (4): G856-63. [PMID:12223345]

2. Greferath U, Brandstätter JH, Wässle H, Kirsch J, Kuhse J, Grünert U. (1994) Differential expression of glycine receptor subunits in the retina of the rat: a study using immunohistochemistry and in situ hybridization. Vis. Neurosci., 11 (4): 721-9. [PMID:7918222]

3. Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H. (1990) Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J., 9 (3): 771-6. [PMID:2155780]

4. Haverkamp S, Müller U, Zeilhofer HU, Harvey RJ, Wässle H. (2004) Diversity of glycine receptors in the mouse retina: localization of the alpha2 subunit. J. Comp. Neurol., 477 (4): 399-411. [PMID:15329889]

5. Kuhse J, Kuryatov A, Maulet Y, Malosio ML, Schmieden V, Betz H. (1991) Alternative splicing generates two isoforms of the alpha 2 subunit of the inhibitory glycine receptor. FEBS Lett., 283 (1): 73-7. [PMID:1645300]

6. Kumar DV, Nighorn A, St John PA. (2002) Role of Nova-1 in regulating alpha2N, a novel glycine receptor splice variant, in developing spinal cord neurons. J. Neurobiol., 52 (2): 156-65. [PMID:12124753]

7. Malosio ML, Marquèze-Pouey B, Kuhse J, Betz H. (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J., 10 (9): 2401-9. [PMID:1651228]

8. Matzenbach B, Maulet Y, Sefton L, Courtier B, Avner P, Guénet JL, Betz H. (1994) Structural analysis of mouse glycine receptor alpha subunit genes. Identification and chromosomal localization of a novel variant. J. Biol. Chem., 269 (4): 2607-12. [PMID:7507926]

9. Miller PS, Harvey RJ, Smart TG. (2004) Differential agonist sensitivity of glycine receptor alpha2 subunit splice variants. Br. J. Pharmacol., 143 (1): 19-26. [PMID:15302677]

10. Nguyen L, Malgrange B, Belachew S, Rogister B, Rocher V, Moonen G, Rigo JM. (2002) Functional glycine receptors are expressed by postnatal nestin-positive neural stem/progenitor cells. Eur. J. Neurosci., 15 (8): 1299-305. [PMID:11994124]

11. Rundström N, Schmieden V, Betz H, Bormann J, Langosch D. (1994) Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels. Proc. Natl. Acad. Sci. U.S.A., 91 (19): 8950-4. [PMID:8090751]

12. Young TL, Cepko CL. (2004) A role for ligand-gated ion channels in rod photoreceptor development. Neuron, 41 (6): 867-79. [PMID:15046720]

13. Young-Pearse TL, Ivic L, Kriegstein AR, Cepko CL. (2006) Characterization of mice with targeted deletion of glycine receptor alpha 2. Mol. Cell. Biol., 26 (15): 5728-34. [PMID:16847326]

Contributors

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How to cite this page

Joseph. W. Lynch.
Glycine receptors: glycine receptor α2 subunit. Last modified on 05/02/2016. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=424.