Nomenclature: GPR88

Family: Class A Orphans

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

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 384 1p21.3 GPR88 G protein-coupled receptor 88 6
Mouse 7 384 3 G1 Gpr88 G-protein coupled receptor 88 6
Rat 7 384 2q41 Gpr88 G-protein coupled receptor 88
Previous and Unofficial Names
Strg
STRG
GPR88
G-protein coupled receptor 88
probable G-protein coupled receptor 88
G protein coupled receptor 88
G protein-coupled receptor 88
striatum-specific G-protein coupled receptor
AW061286
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Tissue Distribution
Brain (caudate putamen, nucleus accumbens, olfactory tubercle, inferior olivary nucleus). Not detected in heart, lung, liver, spleen, kidney, muscle, testis.
Species:  Mouse
Technique:  Northern Blot and in situ hybridisation.
References:  3,6
Striatum, medial division of the central nucleus of amygdala (CeA), piriform cortex. Not detected in the bed nucleus of stria terminalis (BNST).
Species:  Mouse
Technique:  in situ hybridisation
References:  1
Striatum
Species:  Rat
Technique:  RT-PCR
References:  6
GPR88 protein is more concentrated in the striatum than in the cortex. It is undetected in the cerebellum.
Species:  Rat
Technique:  Western Blot
References:  5
Brain with highest expression in the central nucleus of amygdala (CeA). Not detected in spinal cord, thymus, lung, spleen, heart, liver, intestine, stomach, kidney, testis and muscle.
Species:  Rat
Technique:  RT-PCR
References:  1,3
Striatal GPR88 is confined to the somatodendritic compartments of medium spiny neurons (MSNs).
Species:  Rat
Technique:  Ultrastructural immunolabeling
References:  5
Striatum (expression limited to striatal projection medium spiny neurons expressing preprotachykinin, substance P or preproenkephalin mRNAs), olfactory tubercle, nucleus accumbens, rostrocaudal extent of the cerebral neocortex, amygdala and hypothalamus.
Species:  Rat
Technique:  immunohistochemistry
References:  5
Tissue Distribution Comments
GPR88 expression is often associated with vesicular glutamate transporter 1- immunoreactive terminals [5]. Strital GPR88 expression is regulated by dopaminergic and glutamatergic afferents [5].
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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Physiological Functions
Modulates the striatal dopaminergic system
Species:  Mouse
Tissue:  Striatum
References:  4
Physiological Functions Comments
Increased GPR88 expression was observed in the rat arcuate nucleus and ventromedial nucleus of the hypothalamus during lactation [7]. In addition, GPR88 expression was upregulated in the central extended amygdala after repeated mu receptor stimulation [2]. Since mu-opioid receptors are involved in addictive behaviours, it was speculated that GPR88 might be involved in neural adaptations underlying drug addiction and relapse [2]. GPR88 expression in rat hypothalamus was downregulated by sleep deprivation and electroconvulsive therapy and upregulated by fluoxetine treatment.
Physiological Consequences of Altering Gene Expression
Mice with Gpr88 knockout had higher basal striatal phosphorylated DARPP-21-Thr-34 and lower basal dopamine. In addition, mice with Gpr88 knockout displayed disrupted prepulse inhibition of startle (PPI) and increased sensitivity to apomorphineinduced climbing and stereotypy (AICS) and amphetamine-stimulated locomotor activity.
Species:  Mouse
Tissue:  Striatum, nucleus accumbens, layer IV of cortex
Technique:  Gene knockouts
References:  4
Biologically Significant Variants
Type:  SNP
Species:  Human
Change:  V190I
Global MAF (%):  49
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 77|40|28|49
Minor allele count:  G=0.485/1060
SNP accession: 
Validation:  1000 Genomes
Available Assays
DiscoveRx PathHunter® CHO-K1 GPR88 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0357C2A)
PathHunter® eXpress GPR88 CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0357E2ACP1M)
more info

REFERENCES

1. Becker JA, Befort K, Blad C, Filliol D, Ghate A, Dembele D, Thibault C, Koch M, Muller J, Lardenois A, Poch O, Kieffer BL. (2008) Transcriptome analysis identifies genes with enriched expression in the mouse central extended amygdala. Neuroscience156 (4): 950-65. [PMID:18786617]

2. Befort K, Filliol D, Ghate A, Darcq E, Matifas A, Muller J, Lardenois A, Thibault C, Dembele D, Le Merrer J, Becker JA, Poch O, Kieffer BL. (2008) Mu-opioid receptor activation induces transcriptional plasticity in the central extended amygdala. Eur. J. Neurosci.27 (11): 2973-84. [PMID:18588537]

3. Ghate A, Befort K, Becker JA, Filliol D, Bole-Feysot C, Demebele D, Jost B, Koch M, Kieffer BL. (2007) Identification of novel striatal genes by expression profiling in adult mouse brain. Neuroscience146 (3): 1182-92. [PMID:17395390]

4. Logue SF, Grauer SM, Paulsen J, Graf R, Taylor N, Sung MA, Zhang L, Hughes Z, Pulito VL, Liu F, Rosenzweig-Lipson S, Brandon NJ, Marquis KL, Bates B, Pausch M. (2009) The orphan GPCR, GPR88, modulates function of the striatal dopamine system: a possible therapeutic target for psychiatric disorders?. Mol. Cell. Neurosci.42 (4): 438-47. [PMID:19796684]

5. Massart R, Guilloux JP, Mignon V, Sokoloff P, Diaz J. (2009) Striatal GPR88 expression is confined to the whole projection neuron population and is regulated by dopaminergic and glutamatergic afferents. Eur. J. Neurosci.30 (3): 397-414. [PMID:19656174]

6. Mizushima K, Miyamoto Y, Tsukahara F, Hirai M, Sakaki Y, Ito T. (2000) A novel G-protein-coupled receptor gene expressed in striatum. Genomics69 (3): 314-21. [PMID:11056049]

7. Xiao XQ, Grove KL, Lau SY, McWeeney S, Smith MS. (2005) Deoxyribonucleic acid microarray analysis of gene expression pattern in the arcuate nucleus/ventromedial nucleus of hypothalamus during lactation. Endocrinology146 (10): 4391-8. [PMID:16002521]

To cite this database page, please use the following:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR88. Last modified on 09/08/2013. Accessed on 25/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=123.

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