glycine receptor α3 subunit | Glycine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

glycine receptor α3 subunit

Target id: 425

Nomenclature: glycine receptor α3 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 α3 subunit in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 464 4q33-q34 GLRA3 glycine receptor alpha 3 9
Mouse 4 480 8 B2 Glra3 glycine receptor, alpha 3 subunit 5
Rat 4 480 16p11 Glra3 glycine receptor, alpha 3 6
Previous and Unofficial Names
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 = 105 pS (main state); (+ β = 48)
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
HU-210 Hs Antagonist 7.3 pIC50
pIC50 7.3 (IC50 5x10-8 M)
WIN55212-2 Hs Antagonist 7.0 pIC50
pIC50 7.0 (IC50 9.7x10-8 M)
HU-308 Hs Antagonist 7.0 pIC50
pIC50 7.0 (IC50 9.7x10-8 M)
(12E,20Z,18S)-8-hydroxyvariabilin Hs Antagonist 5.2 pIC50
pIC50 5.2 (IC50 7x10-6 M)
nifedipine Hs Antagonist 4.5 pIC50
pIC50 4.5 (IC50 2.92x10-5 M)
strychnine Hs Antagonist - -
[3H]strychnine 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 4.3x10-7 M)
Not voltage dependent
ginkgolide B Hs - no 5.7 pIC50 - no
pIC50 5.7 (IC50 1.8x10-6 M)
Not voltage dependent
picrotin Hs - no 5.2 pIC50 - no
pIC50 5.2 (IC50 6x10-6 M)
Not voltage dependent
picrotoxin Hs - no - - - no
block is weaker when β subunit is co-expressed
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
Δ9-tetrahydrocannabinol Hs Potentiation ~5.3 pEC50 - no
pEC50 ~5.3 (EC50 ~5x10-6 M) ~1500% potentiation
Not voltage dependent
Cu2+ Hs Inhibition 5.0 pIC50 - no
pIC50 5.0 (IC50 9x10-6 M) endogenous
Not voltage dependent
Zn2+ Hs Inhibition 3.8 pIC50 - no
pIC50 3.8 (IC50 1.5x10-4 M) endogenous
Not voltage dependent
Tissue Distribution
Spinal cord (dorsal horn laminae 1 and 2)
Species:  Mouse
Technique:  Immunocytochemistry
References:  3
Retina (bipolar, amacrine and ganglion cells in inner plexiform layer)
Species:  Mouse
Technique:  Immunohistochemistry
References:  4
Retina (entire inner nuclear layer and in cells in the ganglion cell layer)
Species:  Rat
Technique:  In situ hybridisation
References:  2
Cochlea (Organ of Corti, spiral ganaglion neurons)
Species:  Rat
Technique:  RT-PCR
References:  1
Internal granule cell layer of olfactory bulb, infralimbic cortex, hippocampus (CA1, CA3 and dentate gyrus), hypothalamus, cerebellar granule cell layer
Species:  Rat
Technique:  In situ hybridisation
References:  7
Gene Expression and Pathophysiology
GlyR α3 subunit knockout
Tissue or cell type: 
Pathophysiology:  Knockout mice displayed no overt behavioural phenotype. Notably, they did not exhibit startle symptoms and they displayed normal responses to tactile and acute inflammatory pain stimuli. However, mice deficient in GlyR α3 not only lacked the inhibition of glycinergic neurotransmission by prostaglandin E2 seen in wildtype mice but also showed a reduction in pain sensitization induced by spinal prostaglandin E2 injection or peripheral inflammation.
Species:  Mouse
Technique:  Gene targeting 'knockout' in embryonic stem cells
References:  3
Biologically Significant Variants
Type:  mRNA editing
Species:  Rat
Description:  RNA editing results in a novel α3 subunit variant (α3-P185L) at which glycine demonstrates high potency.
References:  8
Type:  Splice variant
Species:  Human
Description:  The GlyR α3L splice variant, contains an additional 15 amino acids in the large intracellular M3-M4 domain relative to the α3K variant. They share similar distribution patterns. The α3K variant displays faster desensitisation.
Amino acids:  479
References:  9
General Comments
Two alternatively spliced human glycine receptor α3 subunits exist, provisionally termed α3L and α3S (or α3K). α3S differs from α3L (tabulated above) by deletion of 15 amino acid residues in the large intracellular loop between TM3 and TM4 [9]. In addition, RNA editing results in a novel α3 subunit (α3P185L) at which glycine demonstrates high agonist potency [8].

References

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1. Dlugaiczyk J, Singer W, Schick B, Iro H, Becker K, Becker CM, Zimmermann U, Rohbock K, Knipper M. (2008) Expression of glycine receptors and gephyrin in the rat cochlea. Histochem. Cell Biol., 129 (4): 513-23. [PMID:18231803]

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. Harvey RJ, Depner UB, Wässle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schütz B, Abo-Salem OM, Zimmer A, Poisbeau P, Welzl H, Wolfer DP, Betz H, Zeilhofer HU, Müller U. (2004) GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science, 304 (5672): 884-7. [PMID:15131310]

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. Kingsmore SF, Suh D, Seldin MF. (1994) Genetic mapping of the glycine receptor alpha 3 subunit on mouse chromosome 8. Mamm. Genome, 5 (12): 831-2. [PMID:7894176]

6. Kuhse J, Schmieden V, Betz H. (1990) Identification and functional expression of a novel ligand binding subunit of the inhibitory glycine receptor. J. Biol. Chem., 265 (36): 22317-20. [PMID:2176214]

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. Meier JC, Henneberger C, Melnick I, Racca C, Harvey RJ, Heinemann U, Schmieden V, Grantyn R. (2005) RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency. Nat. Neurosci., 8 (6): 736-44. [PMID:15895087]

9. Nikolic Z, Laube B, Weber RG, Lichter P, Kioschis P, Poustka A, Mülhardt C, Becker CM. (1998) The human glycine receptor subunit alpha3. Glra3 gene structure, chromosomal localization, and functional characterization of alternative transcripts. J. Biol. Chem., 273 (31): 19708-14. [PMID:9677400]

Contributors

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How to cite this page

Joseph. W. Lynch.
Glycine receptors: glycine receptor α3 subunit. Last modified on 10/11/2014. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=425.