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GPR68

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Not curated in GtoImmuPdb

Target id: 114

Nomenclature: GPR68

Family: Class A Orphans with emerging pharmacology

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

See the Latest Pairings page for more information.

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 7 365 14q32.11 GPR68 G protein-coupled receptor 68 2,34
Mouse 7 365 12 E Gpr68 G protein-coupled receptor 68
Rat 7 375 6q32 Gpr68 G protein-coupled receptor 68
Previous and Unofficial Names Click here for help
GPR12A | Ovarian cancer G-protein coupled receptor 1 | sphingosylphosphorylcholine receptor | OGR1
Database Links Click here for help
Specialist databases
GPCRdb ogr1_human (Hs), ogr1_mouse (Mm)
Other databases
Alphafold Q15743 (Hs), Q8BFQ3 (Mm)
ChEMBL Target CHEMBL3713916 (Hs), CHEMBL4523380 (Mm)
Ensembl Gene ENSG00000119714 (Hs), ENSMUSG00000047415 (Mm), ENSRNOG00000046309 (Rn)
Entrez Gene 8111 (Hs), 238377 (Mm), 314386 (Rn)
Human Protein Atlas ENSG00000119714 (Hs)
KEGG Gene hsa:8111 (Hs), mmu:238377 (Mm), rno:314386 (Rn)
OMIM 601404 (Hs)
Pharos Q15743 (Hs)
RefSeq Nucleotide NM_003485 (Hs), NM_175493 (Mm), NM_001108049 (Rn)
RefSeq Protein NP_003476 (Hs), NP_780702 (Mm), NP_001101519 (Rn)
UniProtKB Q15743 (Hs), Q8BFQ3 (Mm)
Wikipedia GPR68 (Hs)
Natural/Endogenous Ligands Click here for help
Protons
Endogenous ligand
Protons

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
OSTN (115-133) Peptide Hs Agonist 6.4 pEC50 5
⤷ pEC50 6.4 (EC50 3.8x10-7 M) [5]
CARTPT (76-96) {Sp: Human} Peptide Hs Agonist 6.0 pEC50 5
⤷ pEC50 6.0 (EC50 1.05x10-6 M) [5]
Pomc (141-162) Peptide Hs Agonist 5.9 pEC50 5
⤷ pEC50 5.9 (EC50 1.29x10-6 M) [5]
Agonist Comments
Gpr68 was previously identified as a receptor for sphingosyl phosphorylcholine (SPC) [35], but the original publication has been retracted [39]. However, GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton-sensing receptors detecting acidic pH [4,28]. SPC was later found to antagonise the proton-induced activation of the GPR68-mediated signalling pathways [21,28]. A family of 3,5-disubstituted isoxazoles (Isx) were identified as agonists of GPR68 [26].
Antagonist Comments
It has been reported by Wang et al. that psychosine antagonises pH responses by GPR68 [32].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MS48107 Small molecule or natural product Primary target of this compound Hs Positive 5.8 pKB 37
⤷ pKB 5.8 (KB 1.412x10-6 M) [37]
ogerin Small molecule or natural product Hs Positive 5.0 pKB 10
⤷ pKB 5.0 (KB 1.071x10-5 M) [10]
Description: Allosteric ligand biochemical binding affinity in the presence of protons (H+. Affinity cannot be measured in the absence of endogenous ligand for this receptor.
lorazepam Small molecule or natural product Approved drug Hs Positive - - 10
⤷ lorazepam characterised as a non-selective GPR68 positive allosteric modulator for the agonist proton in cAMP production [10]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family 		Adenylyl cyclase inhibition
Phospholipase C stimulation
References:  17,19,33,36
Tissue Distribution Click here for help
Spleen, testis, small intestine, peripheral blood leukocytes, brain, heart, lung, placenta and kidney. Not detected in thymus, prostate, ovary, colon, liver, skeletal muscle and pancreas.
Species:  Human
Technique:  Northen blot
References:  34
Human thyroid cancer cells (FRO cells) and normal human thyroid cells
Species:  Human
Technique:  RT-PCR
References:  1
Aortic smooth muscle cells
Species:  Human
Technique:  RT-PCR
References:  17,30
Expressed in the αβ Jurkat and the γδ PEER T cell lines, the B cell lines RAJI and DAUDI, the myelogenous cell line K562 and IL-2-activated NK cells. Absent in CD16- and CD16+ resting NK cells.
Species:  Human
Technique:  RT-PCR
References:  12
Expressed in IL-12-and IL-15-activated NK cells, but not in IFN-α-activated cells.
Species:  Human
Technique:  RT-PCR
References:  12
Airway smooth muscle
Species:  Human
Technique:  RT-PCR
References:  11,27
Abundantly expressed in lung. Also present in the placenta, spleen and testis.
Species:  Human
Technique:  Northen blot
References:  2
Osteosarcoma cells and primary osteoblast precursors
Species:  Human
Technique:  RT-PCR
References:  18
Human cerebellar granule cell tumor cell line and primary human medulloblastoma tissue
Species:  Human
Technique:  RT-PCR
References:  9
Differentiated HL-60 neutrophil-like cells and human neutrophils
Species:  Human
Technique:  RT-PCR
References:  23
Peritoneal macrophage
Species:  Mouse
Technique:  RT-PCR
References:  20
Thymocytes
Species:  Mouse
Technique:  RT-PCR
References:  32
Primary calvarial cells
Species:  Mouse
Technique:  RT-PCR
References:  7
Spleen, bladder, heart, small intestine, kidney, liver, lung, skeletal muscle, stomach, testis, cerebrum, brain stem, cerebellum, spinal cord, dorsal root ganglion, trigeminal ganglion.
Species:  Mouse
Technique:  RT-PCR
References:  8
Dorsal root ganglion, and mostly expressed in small-diameter neurons
Species:  Mouse
Technique:  in situ hybridisation
References:  8
Lung, testis, heart, brain, spleen, thymus, brown fat, small intestine, colon, peripheral blood leukocytes, macrophages, stomach, ovary, white fat and prostate. Not detected in liver, kidney and skeletal muscle.
Species:  Mouse
Technique:  RT-PCR
References:  16
Newborn myocardium, postnatal and injury-activated subepicardium, myocardial infarction-spared cardiomyocytes
Species:  Mouse
Technique:  Immunohistochemistry
References:  26
Proximal tubules and collecting duct of mouse nephrons
Species:  Mouse
Technique:  RT-PCR
References:  22
Cuboidal/columnar epithelial cells covering the large airways of the lung and vascular smooth muscles surrounding blood vessel in the lung.
Species:  Mouse
Technique:  Immunohistochemistry
References:  16
Osteoclast
Species:  Rat
Technique:  Immunofluorescence
References:  13
Osteoblasts, osteocytes, chondrocytes of hypertrophic cartilage, epithelial cells of the lung, intestine, renal tubules, skeletal myocytes, hepatocytes
Species:  Rat
Technique:  immunohistochemistry
References:  18
Tissue Distribution Comments
GPR68 was expressed early during mouse osteoclast differentiation in vivo and in vitro [36]. GPR68 was strongly regulated in vivo after 2 days of colony stimulating factor-1 treatment [36]. High levels of GPR68 mRNA were detected by microarray, RT-PCR and immunoblotting when mouse bone marrow mononuclear cells and RAW 264.7 pre-osteoclast-like cells were treated with RANKL to induce osteoclast differentiation [13,36].
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
Acts as pH sensor and mediates calcium release from the bone during metabolic acidosis.
Species:  Mouse
Tissue:  Bone cells
References:  6-7
Acts as a proton-sensing receptor stimulating inositol phosphate formation and subsequently intracellular calcium mobilisation.
Species:  Human
Tissue:  HEK293 cells
References:  18
Involved in acidic pH-stimulated connective tissue growth factor (CTGF) production in human airway smooth muscle cells.
Species:  Human
Tissue:  Airway smooth muscle cells
References:  19
Involved in acidification-stimulated IL-6 production and Ca2+ mobilisation in human airway smooth muscle cells.
Species:  Human
Tissue:  Airway smooth muscle cells
References:  11
Regulate the activity of two-proton transport system, NHE3 and H+-ATPase.
Species:  Mouse
Tissue:  Proximal tubules
References:  22
Regulate osteoblastic COX-2 induction and PGE2 production in response to acidic pH via GPR68/Gq/phospholipase C/protein kinase C pathway.
Species:  Human
Tissue:  Osteoblastic cell line
References:  31
Physiological Functions Comments
GPR68 transiently increases intracellular calcium, mediates SPC-induced ERK1/2 activation and inhibits cellular proliferation [3]. GPR68 causes cAMP accumulation and inositol phosphate production upon stimulation by extracellular acidification [21].
Physiological Consequences of Altering Gene Expression Click here for help
Overexpression of GPR68 enhances SPC-induced activation of ERK1/2.
Species:  Human
Tissue:  HEK 293 cells
Technique:  Gene knockout
References:  3
Expression of GPR68 in vitro inhibits cell migration via Gi activation and the secretion of a hydrophobic factor.
Species:  Human
Tissue:  PC3 cells (Human prostate cancer cells)
Technique:  Gene overexpression
References:  17
Reduction of metastases was observed in mice when PC3 cells with expression of exogenous GPR68 were injected into mice.
Species:  Mouse
Tissue:  Prostate cancer cell
Technique:  Gene overexpression
References:  17
The acid-induced inositol phosphate production, [Ca2+]i increase, cAMP accumulation and prostaglandin I2 production in human aortic smooth muscle cells were inhibited by GPT68 siRNA.
Species:  Human
Tissue:  Aortic smooth muscle cells
Technique:  RNA interference
References:  29
Acid-induced rise of [Ca2+]i was inhibited in osteoclast-like cells.
Species:  Mouse
Tissue:  RAW 264.7 cell
Technique:  RNA interference
References:  24
Small interfering RNA directed against GPR68 inhibits acidification-induced PGI2 production, COX-2 induction and MAPK phosphatase-1 expression in human aortic smooth muscle cells.
Species:  Human
Tissue:  Aortic smooth muscle cells
Technique:  RNA interference
References:  17
Mice with GPR68 knockout show upregulated expression of Pyk2 and a significant increase in sodium-hydrogen antiporter (NHE) activity.
Species:  Mouse
Tissue:  Proximal tubules
Technique:  Gene knockout
References:  22
Proton-induced COX-2 protein expression and PGE2 production were markedly inhibited in osteoblast with GPR68 knockdown.
Species:  Human
Tissue:  Osteoblastic cell line
Technique:  RNA interference
References:  31
Reduced osteoblasts and decreased melanoma cell tumorigenesis were observed in Gpr68 deficient mice.
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  16
RANKL-induced differentiation of both mouse bone marrow mononuclear cells and RAW 264.7 pre-osteoclast-like cells is inhibited in vitro.
Species:  Mouse
Tissue:  Bone marrow cells and pre-osteoclast-like cells
Technique:  RNA interference and anti-GPR immunofluorescence
References:  36
Overexpression of GPR68 in human ovarian cancer cells inhibits cell proliferation and migration, but enhances cell adhesion to the extracellular matrix.
Species:  Human
Tissue:  HEY cells (human ovarian carcinoma cell line)
Technique:  Gene overexpression
References:  25
Physiological Consequences of Altering Gene Expression Comments
Knockout of GPR68 in mouse macrophages did not affect the acidic pH-induced inhibitory action on cytokine production [20].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0002971 abnormal brown adipose tissue morphology PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0002971 abnormal brown adipose tissue morphology PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0002451 abnormal macrophage physiology PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0002451 abnormal macrophage physiology PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
B6.Cg-Gpr68		 MGI:2441763  MP:0008396 abnormal osteoclast differentiation PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0008396 abnormal osteoclast differentiation PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0008396 abnormal osteoclast differentiation PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
B6.Cg-Gpr68		 MGI:2441763  MP:0001541 abnormal osteoclast physiology PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0001541 abnormal osteoclast physiology PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0001541 abnormal osteoclast physiology PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0001780 decreased brown adipose tissue amount PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0003884 decreased macrophage cell number PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0000223 decreased monocyte cell number PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
B6.Cg-Gpr68		 MGI:2441763  MP:0003447 decreased tumor growth/size PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0003447 decreased tumor growth/size PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0000005 increased brown adipose tissue amount PMID: 19479052 
Gpr68tm1.1Yaxu Gpr68tm1.1Yaxu/Gpr68tm1.1Yaxu
involves: 129S4/SvJae * C57BL/6 * FVB/N		 MGI:2441763  MP:0000220 increased monocyte cell number PMID: 19479052 
Gpr68tm1Yaxu Gpr68tm1Yaxu/Gpr68tm1Yaxu
involves: C57BL/6		 MGI:2441763  MP:0003721 increased tumor growth/size PMID: 19479052 
Gene Expression and Pathophysiology Comments
GPR68 expression was shown to be fivefold lower in metastatic prostate cancers than primary prostate cancers [15]. Gene expression of GPR68 is changed in ASIC3 knockout mice [8]. GPR68 has been reported as a novel metastasis suppressor gene for prostate cancer [17].
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  F359S
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 2
Minor allele count:  G=0.005/11
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  rs151219229
Validation:  1000 Genomes
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  R53Q
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  rs2230339
General Comments
GPR68 is fully activated at pH 6.8, but almost silent at pH 7.8 [18]. Several His residues that reside in the extracellular domain of GPR68 are shown to be responsible for the proton binding, pH-sensing activity of GPR68 [18]. GPR68 forms very weak homodimers and relatively weak heterodimers with other receptors (LPA and GPR4) [38]. GPR68 is coupled to IP3-mediated Cai signalling in osteoblasts [14].

References

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1. Afrasiabi E, Blom T, Ekokoski E, Tuominen RK, Törnquist K. (2006) Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C. Cell Signal, 18 (10): 1671-8. [PMID:16490345]

2. An S, Tsai C, Goetzl EJ. (1995) Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue. FEBS Lett, 375 (1-2): 121-4. [PMID:7498459]

3. Bektas M, Barak LS, Jolly PS, Liu H, Lynch KR, Lacana E, Suhr KB, Milstien S, Spiegel S. (2003) The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Biochemistry, 42 (42): 12181-91. [PMID:14567679]

4. Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR et al.. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev, 65 (3): 967-86. [PMID:23686350]

5. Foster SR, Hauser AS, Vedel L, Strachan RT, Huang XP, Gavin AC, Shah SD, Nayak AP, Haugaard-Kedström LM, Penn RB et al.. (2019) Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors. Cell, 179 (4): 895-908.e21. [PMID:31675498]

6. Frick KK, Bushinsky DA. (2010) Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts. Am J Physiol Renal Physiol, 299 (2): F418-25. [PMID:20504884]

7. Frick KK, Krieger NS, Nehrke K, Bushinsky DA. (2009) Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res, 24 (2): 305-13. [PMID:18847331]

8. Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH. (2007) Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci, 36 (2): 195-210. [PMID:17720533]

9. Huang WC, Swietach P, Vaughan-Jones RD, Ansorge O, Glitsch MD. (2008) Extracellular acidification elicits spatially and temporally distinct Ca2+ signals. Curr Biol, 18 (10): 781-5. [PMID:18485712]

10. Huang XP, Karpiak J, Kroeze WK, Zhu H, Chen X, Moy SS, Saddoris KA, Nikolova VD, Farrell MS, Wang S et al.. (2015) Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. Nature, 527 (7579): 477-83. [PMID:26550826]

11. Ichimonji I, Tomura H, Mogi C, Sato K, Aoki H, Hisada T, Dobashi K, Ishizuka T, Mori M, Okajima F. (2010) Extracellular acidification stimulates IL-6 production and Ca(2+) mobilization through proton-sensing OGR1 receptors in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol, 299 (4): L567-77. [PMID:20656891]

12. Jin Y, Damaj BB, Maghazachi AA. (2005) Human resting CD16-, CD16+ and IL-2-, IL-12-, IL-15- or IFN-alpha-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor. Eur J Immunol, 35 (9): 2699-708. [PMID:16078278]

13. Komarova SV, Pereverzev A, Shum JW, Sims SM, Dixon SJ. (2005) Convergent signaling by acidosis and receptor activator of NF-kappaB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts. Proc Natl Acad Sci USA, 102 (7): 2643-8. [PMID:15695591]

14. Krieger NS, Bushinsky DA. (2011) Pharmacological inhibition of intracellular calcium release blocks acid-induced bone resorption. Am J Physiol Renal Physiol, 300 (1): F91-7. [PMID:21048027]

15. LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V, Gerald WL. (2002) Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res, 62 (15): 4499-506. [PMID:12154061]

16. Li H, Wang D, Singh LS, Berk M, Tan H, Zhao Z, Steinmetz R, Kirmani K, Wei G, Xu Y. (2009) Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1. PLoS ONE, 4 (5): e5705. [PMID:19479052]

17. Liu JP, Komachi M, Tomura H, Mogi C, Damirin A, Tobo M, Takano M, Nochi H, Tamoto K, Sato K, Okajima F. (2010) Ovarian cancer G protein-coupled receptor 1-dependent and -independent vascular actions to acidic pH in human aortic smooth muscle cells. Am J Physiol Heart Circ Physiol, 299 (3): H731-42. [PMID:20622109]

18. Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K. (2003) Proton-sensing G-protein-coupled receptors. Nature, 425 (6953): 93-8. [PMID:12955148]

19. Matsuzaki S, Ishizuka T, Yamada H, Kamide Y, Hisada T, Ichimonji I, Aoki H, Yatomi M, Komachi M, Tsurumaki H et al.. (2011) Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells. Biochem Biophys Res Commun, 413 (4): 499-503. [PMID:21907704]

20. Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, Kimura T, Ishizuka T, Sasaki T, Sato T, Kihara Y, Ishii S, Harada A, Okajima F. (2009) Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. J Immunol, 182 (5): 3243-51. [PMID:19234222]

21. Mogi C, Tomura H, Tobo M, Wang JQ, Damirin A, Kon J, Komachi M, Hashimoto K, Sato K, Okajima F. (2005) Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation. J Pharmacol Sci, 99 (2): 160-7. [PMID:16210776]

22. Mohebbi N, Benabbas C, Vidal S, Daryadel A, Bourgeois S, Velic A, Ludwig MG, Seuwen K, Wagner CA. (2012) The proton-activated G protein coupled receptor OGR1 acutely regulates the activity of epithelial proton transport proteins. Cell Physiol Biochem, 29 (3-4): 313-24. [PMID:22508039]

23. Murata N, Mogi C, Tobo M, Nakakura T, Sato K, Tomura H, Okajima F. (2009) Inhibition of superoxide anion production by extracellular acidification in neutrophils. Cell Immunol, 259 (1): 21-6. [PMID:19539899]

24. Pereverzev A, Komarova SV, Korcok J, Armstrong S, Tremblay GB, Dixon SJ, Sims SM. (2008) Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway. Bone, 42 (1): 150-61. [PMID:17964236]

25. Ren J, Zhang L. (2011) Effects of ovarian cancer G protein coupled receptor 1 on the proliferation, migration, and adhesion of human ovarian cancer cells. Chin Med J, 124 (9): 1327-32. [PMID:21740742]

26. Russell JL, Goetsch SC, Aguilar HR, Coe H, Luo X, Liu N, van Rooij E, Frantz DE, Schneider JW. (2012) Regulated expression of pH sensing G Protein-coupled receptor-68 identified through chemical biology defines a new drug target for ischemic heart disease. ACS Chem Biol, 7 (6): 1077-83. [PMID:22462679]

27. Saxena H, Deshpande DA, Tiegs BC, Yan H, Battafarano RJ, Burrows WM, Damera G, Panettieri RA, Dubose TD, An SS et al.. (2012) The GPCR OGR1 (GPR68) mediates diverse signalling and contraction of airway smooth muscle in response to small reductions in extracellular pH. Br J Pharmacol, 166 (3): 981-90. [PMID:22145625]

28. Seuwen K, Ludwig MG, Wolf RM. (2006) Receptors for protons or lipid messengers or both?. J Recept Signal Transduct Res, 26 (5-6): 599-610. [PMID:17118800]

29. Tomura H, Mogi C, Sato K, Okajima F. (2005) Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors. Cell Signal, 17 (12): 1466-76. [PMID:16014326]

30. Tomura H, Wang JQ, Komachi M, Damirin A, Mogi C, Tobo M, Kon J, Misawa N, Sato K, Okajima F. (2005) Prostaglandin I(2) production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells. J Biol Chem, 280 (41): 34458-64. [PMID:16087674]

31. Tomura H, Wang JQ, Liu JP, Komachi M, Damirin A, Mogi C, Tobo M, Nochi H, Tamoto K, Im DS, Sato K, Okajima F. (2008) Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line. J Bone Miner Res, 23 (7): 1129-39. [PMID:18302504]

32. Wang JQ, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F. (2004) TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. J Biol Chem, 279 (44): 45626-33. [PMID:15326175]

33. Xu Y. (2002) Sphingosylphosphorylcholine and lysophosphatidylcholine: G protein-coupled receptors and receptor-mediated signal transduction. Biochim Biophys Acta, 1582 (1-3): 81-8. [PMID:12069813]

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