GABA<sub>B2</sub> | GABA<sub>B</sub> receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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GABAB2

Target id: 241

Nomenclature: GABAB2

Family: GABAB 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 GABAB2 in GtoImmuPdb

Quaternary Structure: Complexes
GABAB receptor
Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 941 9q22.1-22.3 GABBR2 gamma-aminobutyric acid type B receptor subunit 2 12,15
Mouse 7 - 4 B1 Gabbr2 gamma-aminobutyric acid (GABA) B receptor, 2
Rat 7 940 5q24 Gabbr2 gamma-aminobutyric acid type B receptor subunit 2
Previous and Unofficial Names
GABABR2 [8-9,12,19] | GABABR2 | HG20 | G protein-coupled receptor 51 | GABA-B R2 receptor | GABA-B receptor 2 | GPR51 [14,16] | GPRC3B | gamma-aminobutyric acid (GABA) B receptor, 2 | gamma-aminobutyric acid (GABA) B receptor 2 | gamma-aminobutyric acid (GABA) B receptor
Database Links
Specialist databases
GPCRDB gabr2_human (Hs), gabr2_mouse (Mm), gabr2_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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

Agonist Comments
No evidence of any ligand activating GABAB receptors acting on this subunit. It has been proposed, based on evolutionary trace analysis, that no endogenous ligand binds to GABAB2 within the equivalent site of GABAB1 where agonists act [10].
Antagonist Comments
So far all competitive antagonists acting at the GABAB heteromeric receptor have been shown to interact exclusively with the GABAB1 subunit.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CGP7930 Rn Positive 6.7 pEC50 1,17
pEC50 6.7 [1,17]
Allosteric Modulator Comments
CGP7930 is acting as a positive allosteric regulator of the heteromeric GABAB1 - GABAB2 receptor. This compound has been shown to act in the GABAB2 heptahelical domain [1].
GS 39783 has also been shown to be a selective positive allosteric regulator in rats [18]
Primary Transduction Mechanisms
Comments:  The GABAB2 subunit has been shown not to couple to G proteins efficiently when in the absence of GABAB1. However, the GABAB2 subunit contains all the molecular determinants required for G protein recognition and activation by the heterodimer.
References:  2,7
Tissue Distribution
Brain: thalamus, cerebral cortex > amygdala, hippocampus, cerebellum, occipital pole, frontal lobe, temporal lobe > caudate nucleus, corpus collosum, substantia nigra, subthalamic nucleus, medulla, putamen.
Weak expression in the spinal cord.
Very weak expression in the heart.
Species:  Human
Technique:  Northern blotting.
References:  5
Hippocampus, medial habernula, thalamus and cerebellum.
Species:  Rat
Technique:  in situ hybridisation.
References:  8
High levels in the cortex, thalamus, medial and lateral habenula and cerebellum.
In contrast to GABAB1, GABAB2 is virtually absent from the caudate/putamen, and has lower levels in the medial basal hypothalamus, septum and brainstem.
Absent in white matter (therefore exclusive to neurons).
Species:  Rat
Technique:  in situ hybridisation.
References:  5
Brain: neocortex, hippocampus, thalamus, cerebellum and habenula. Spinal cord: superficial layers of the dorsal horn and motor neurones in the deep layers of the ventral horn.
Species:  Rat
Technique:  Immunohistochemistry.
References:  4
Brain: Most predominant in the piriform cortex, hippocampus (particularly CA2/CA3 regions and dentate gyrus) and medial habenula > all layers of the cerebral cortex, thalamus and cerebellar purkinje cells > several hypothalamic and brainstem nuclei.
Only weak expression in the basal ganglia, olfactory tubercle and hypothalamus.
Moderate expression in the peripheral ganglia.
Low expression in the spinal cord.
Species:  Rat
Technique:  in situ hybridisation.
References:  6
Tissue Distribution Comments
GABAB2 has a similar distribution to GABAB1 in the brain except that GABAB2 levels are low in the caudate putamen, hypothalamus, olfactory bulb [3-6,8,11] and in the E11-E17 mouse embryo [13], unlike GABAB1.

Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assay Comments
So far there is no evidence for the formation of a functional receptor made up exclusively of the GABAB2 subunit.

Physiological Functions Comments
So far, there is no indication that a function may be generated exclusively by the GABAB2 subunit, in the absence of GABAB1.

Although the GABAB2 subunit can be considered as an orphan subunit since it does not appear to bind any endogenous ligand, its function as a necessary subunit for the formation of a fully functional GABAB heterodimeric receptor is now well established.
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0004994 abnormal brain wave pattern PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0003360 abnormal depression-related behavior PMID: 15706241 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0002572 abnormal emotion/affect behavior PMID: 15240800 
Gabbr2+|Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2+
BALB/c-Gabbr2
MGI:2386030  MP:0002572 abnormal emotion/affect behavior PMID: 15706241 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0002910 abnormal excitatory postsynaptic currents PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0002945 abnormal inhibitory postsynaptic currents PMID: 15240800 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0002945 abnormal inhibitory postsynaptic currents PMID: 15451409 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0002911 abnormal inhibitory postsynaptic potential PMID: 15451409 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0002272 abnormal nervous system electrophysiology PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0003635 abnormal synaptic transmission PMID: 15706241 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0001968 abnormal touch/ nociception PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0003996 clonic seizures PMID: 15240800 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0001262 decreased body weight PMID: 15451409 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0003998 decreased thermal nociceptive threshold PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0001399 hyperactivity PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0002738 hyperresponsive to tactile stimuli PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0009747 impaired behavioral response to xenobiotic PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0004000 impaired passive avoidance behavior PMID: 15240800 
Gabbr2tm1Bet Gabbr2tm1Bet/Gabbr2tm1Bet
BALB/c-Gabbr2
MGI:2386030  MP:0001363 increased anxiety-related response PMID: 15706241 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0002083 premature death PMID: 15451409 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0002064 seizures PMID: 15451409 
Gabbr2tm1Arca Gabbr2tm1Arca/Gabbr2tm1Arca
involves: 129P2/OlaHsd
MGI:2386030  MP:0003997 tonic-clonic seizures PMID: 15451409 

References

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1. Binet V, Brajon C, Le Corre L, Acher F, Pin JP, Prezeau L. (2004) The heptahelical domain of GABA(B2) is activated directly by CGP7930, apositive allosteric modulator of the GABA(B) receptor. J Biol Chem., 279: 29085-29091. [PMID:15126507]

2. Bowery NG. (1993) GABAB receptor pharmacology. Annu. Rev. Pharmacol. Toxicol., 33: 109-147. [PMID:8388192]

3. Bowery NG, Hudson AL, Price GW. (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience, 20: 365-383. [PMID:3035421]

4. Charles KJ, Evans ML, Robbins MJ, Calver AR, Leslie RA, Pangalos MN. (2001) Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) andGABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion. Neuroscience, 106: 447-467. [PMID:11591450]

5. Clark JA, Mezey E, Lam AS, Bonner TI. (2000) Distribution of the GABA(B) receptor subunit gb2 in rat CNS. Brain Res., 860: 41-52. [PMID:10727622]

6. Durkin MM, Gunwaldsen CA, Borowsky B, Jones KA, Branchek TA. (1999) An in situ hybridization study of the distribution of the GABA(B2) protein mRNAin the rat CNS. Brain Res Mol Brain Res., 71: 185-200. [PMID:10521573]

7. Hill DR. (1985) GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br. J. Pharmacol., 84: 249-257. [PMID:2579700]

8. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C. (1998) GABAB receptors function as a heteromeric assembly of the subunits GABABR1 and GABABR2. Nature, 396: 674-679. [PMID:9872315]

9. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B. (1998) GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature, 396: 683-687. [PMID:9872317]

10. Kniazeff J, Galvez T, Labesse G, Pin JP. (2002) No ligand binding in the GB2 subunit of the GABA(B) receptor is required foractivation and allosteric interaction between the subunits. J Neurosci., 22: 7352-7361. [PMID:12196556]

11. Margeta-Mitrovic M, Mitrovic I, Riley RC Jan LY, Basbaum AI. (1999) Immunohistochemical localization of GABAB receptors in the rat central nervous system. J. Comp. Neurol., 405: 299-321. [PMID:10076927]

12. Martin SC, Russek SJ, Farb DH. (1999) Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci, 13: 180-191. [PMID:10328880]

13. Martin SC, Steiger JL, Gravielle MC, Lyons HR, Russek SJ, Farb DH. (2004) Differential expression of gamma-aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons. J Comp Neurol, 473: 16-29. [PMID:15067715]

14. Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, Tabaton M, Robello M, Gatta E, Russo C et al.. (2011) 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol. Dis., 41 (2): 308-17. [PMID:20888417]

15. Ng GY, McDonald T, Bonnert T, Rigby M, Heavens R, Whiting P, Chateauneuf A, Coulombe N, Kargman S, Caskey T, Evans J, O'Neill G P, Liu Q. (1999) Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9. Genomics, 56: 288-295. [PMID:10087195]

16. Sun D, Huang W, Hwang YY, Zhang Y, Zhang Q, Li MD. (2007) Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions. Neuropsychopharmacology, 32 (1): 110-6. [PMID:16794563]

17. Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K. (2001) Positive allosteric modulation of native and recombinant gamma-aminobutyricacid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol(CGP7930) and its aldehyde analog CGP13501. Mol Pharmacol., 60: 963-971. [PMID:11641424]

18. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K. (2003) N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783)and structurally related compounds: novel allosteric enhancers ofgamma-aminobutyric acidB receptor function. J Pharmacol Exp Ther., 307: 322-330. [PMID:12954816]

19. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH. (1998) Heterodimerization is required for the formation of a functional GABAB receptor. Nature, 396: 679-682. [PMID:9872316]

Contributors

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How to cite this page

Bernhard Bettler, Norman G. Bowery, John F. Cryan, Sam J. Enna, David H. Farb, Wolfgang Foestl, Klemens Kaupmann, Jean-Philippe Pin.
GABAB receptors: GABAB2. Last modified on 20/02/2018. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=241.