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GPR88

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Not curated in GtoImmuPdb

Target id: 123

Nomenclature: GPR88

Family: Class A Orphans with only surrogate ligands

Annotation status:  image of a blue circle Annotated and reviewed, awaiting update  » Email us

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 384 1p21.2 GPR88 G protein-coupled receptor 88 9
Mouse 7 384 3 G1 Gpr88 G-protein coupled receptor 88 9
Rat 7 384 2q41 Gpr88 G-protein coupled receptor 88
Previous and Unofficial Names Click here for help
STRG | striatum-specific G-protein coupled receptor
Database Links Click here for help
Specialist databases
GPCRdb gpr88_human (Hs), gpr88_mouse (Mm), gpr88_rat (Rn)
Other databases
Alphafold Q9GZN0 (Hs), Q9EPB7 (Mm), Q9ESP4 (Rn)
ChEMBL Target CHEMBL3399910 (Hs), CHEMBL3879835 (Mm)
Ensembl Gene ENSG00000181656 (Hs), ENSMUSG00000068696 (Mm), ENSRNOG00000026953 (Rn)
Entrez Gene 54112 (Hs), 64378 (Mm), 64443 (Rn)
Human Protein Atlas ENSG00000181656 (Hs)
KEGG Gene hsa:54112 (Hs), mmu:64378 (Mm), rno:64443 (Rn)
OMIM 607468 (Hs)
Pharos Q9GZN0 (Hs)
RefSeq Nucleotide NM_022049 (Hs), NM_022427 (Mm), NM_031696 (Rn)
RefSeq Protein NP_071332 (Hs), NP_071872 (Mm), NP_113884 (Rn)
UniProtKB Q9GZN0 (Hs), Q9EPB7 (Mm), Q9ESP4 (Rn)
Wikipedia GPR88 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RTI-122 Small molecule or natural product Hs Agonist 8.0 pEC50 10
⤷ pEC50 8.0 (EC50 1.1x10-8 M) [10]
Description: Agonist potency determined in a TR-FRET cAMP assay using CHO cells expressing hGPR88
RTI-13951-33 Small molecule or natural product Primary target of this compound Hs Agonist 7.6 pEC50 6
⤷ pEC50 7.6 (EC50 2.5x10-8 M) [6]
Description: In an in vitro cAMP functional assay.
compound 2 [PMID: 24793972] Small molecule or natural product Ligand has a PDB structure Hs Full agonist 6.2 pEC50 5
⤷ pEC50 6.2 (EC50 6x10-7 M) [5]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
References:  3,5,11
Tissue Distribution Click here for help
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
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:  4,9
Striatum
Species:  Rat
Technique:  RT-PCR
References:  9
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:  1,4
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:  8
GPR88 protein is more concentrated in the striatum than in the cortex. It is undetected in the cerebellum.
Species:  Rat
Technique:  Western Blot
References:  8
Striatal GPR88 is confined to the somatodendritic compartments of medium spiny neurons (MSNs).
Species:  Rat
Technique:  Ultrastructural immunolabeling
References:  8
Tissue Distribution Comments
GPR88 expression is often associated with vesicular glutamate transporter 1- immunoreactive terminals [8]. Strital GPR88 expression is regulated by dopaminergic and glutamatergic afferents [8].
Expression Datasets Click here for help

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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 Click here for help
Modulates the striatal dopaminergic system
Species:  Mouse
Tissue:  Striatum
References:  7
Physiological Functions Comments
Increased GPR88 expression was observed in the rat arcuate nucleus and ventromedial nucleus of the hypothalamus during lactation [12]. 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 Click here for help
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:  7
Gene Expression and Pathophysiology Comments
Gene disruption results in altered striatal signalling [7].
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  V190I
Global MAF (%):  49
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 77|40|28|49
Minor allele count:  G=0.485/1060
SNP accession:  VAR_054767, rs2809819
Validation:  1000 Genomes

References

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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. Neuroscience, 156 (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. Dzierba CD, Bi Y, Dasgupta B, Hartz RA, Ahuja V, Cianchetta G, Kumi G, Dong L, Aleem S, Fink C et al.. (2015) Design, synthesis, and evaluation of phenylglycinols and phenyl amines as agonists of GPR88. Bioorg Med Chem Lett, 25 (7): 1448-52. [PMID:25690789]

4. 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. Neuroscience, 146 (3): 1182-92. [PMID:17395390]

5. Jin C, Decker AM, Huang XP, Gilmour BP, Blough BE, Roth BL, Hu Y, Gill JB, Zhang XP. (2014) Synthesis, pharmacological characterization, and structure-activity relationship studies of small molecular agonists for the orphan GPR88 receptor. ACS Chem Neurosci, 5 (7): 576-87. [PMID:24793972]

6. Jin C, Decker AM, Makhijani VH, Besheer J, Darcq E, Kieffer BL, Maitra R. (2018) Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake. J Med Chem, 61 (15): 6748-6758. [PMID:30011199]

7. 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]

8. 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]

9. Mizushima K, Miyamoto Y, Tsukahara F, Hirai M, Sakaki Y, Ito T. (2000) A novel G-protein-coupled receptor gene expressed in striatum. Genomics, 69 (3): 314-21. [PMID:11056049]

10. Rahman MT, Decker AM, Ben Hamida S, Perrey DA, Chaminda Lakmal HH, Maitra R, Darcq E, Kieffer BL, Jin C. (2023) Improvement of the Metabolic Stability of GPR88 Agonist RTI-13951-33: Design, Synthesis, and Biological Evaluation. J Med Chem, 66 (4): 2964-2978. [PMID:36749855]

11. Watkins LR, Orlandi C. (2021) In vitro profiling of orphan G protein coupled receptor (GPCR) constitutive activity. Br J Pharmacol, 178 (15): 2963-2975. [PMID:33784795]

12. 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. Endocrinology, 146 (10): 4391-8. [PMID:16002521]

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Last modified on 16/07/2025.

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