DP2 receptor

Target id: 339

Nomenclature: DP2 receptor

Family: Prostanoid receptors

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

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 395 11q12-q13.3 PTGDR2 prostaglandin D2 receptor 2 15
Mouse 7 382 19 A Ptgdr2 prostaglandin D2 receptor 2 1,9
Rat 7 403 1q43 Ptgdr2 prostaglandin D2 receptor 2 20
Previous and Unofficial Names
Names References
CRTH2 19
CD294
G protein-coupled receptor 44
prostaglandin D2 receptor 2
PGD2 receptor
Gpr44
Database Links
Specialist databases
GPCRDB pd2r2_human (Hs), pd2r2_mouse (Mm), pd2r2_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
PGD2
PGE2
PGF
PGI2
PGJ2
Comments: 11-Dehydro-thromboxane B2, a breakdown product of thromboxane A2 is an additional endogenous agonist of this receptor
Potency order of endogenous ligands
PGD2 >> PGF, PGE2 > PGI2, thromboxane A2

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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]PGD2 Hs Full agonist 7.8 – 8.2 pKd 13,20
pKd 7.8 – 8.2 (Kd 1.6x10-8 – 6x10-9 M) [13,20]
[3H]PGD2 Rn Full agonist 8.0 pKd 20
pKd 8.0 [20]
L-888,607 Hs Full agonist 9.1 pKi 7
pKi 9.1 (Ki 8x10-10 M) [7]
15(R)-15-methyl-PGD2 Hs Full agonist 8.9 pKi 9,14,22
pKi 8.9 [9,14,22]
15-deoxy-Δ12,14-PGJ2 Hs Full agonist 8.5 pKi 19
pKi 8.5 [19]
Δ12-PGJ2 Hs Full agonist 8.2 pKi 19
pKi 8.2 [19]
PGJ2 Hs Full agonist 8.2 pKi 19
pKi 8.2 [19]
PGD2 Hs Full agonist 7.6 – 8.6 pKi 19,22
pKi 7.6 – 8.6 [19,22]
13,14-dihydro-15-keto-PGD2 Hs Full agonist 7.4 – 8.5 pKi 9,19,22
pKi 7.4 – 8.5 (Ki 3.98x10-8 – 3.16x10-9 M) [9,19,22]
15-deoxy-Δ12,14-PGJ2 Mm Full agonist 7.6 pKi 9
pKi 7.6 [9]
13,14-dihydro-15-keto-PGD2 Mm Full agonist 7.5 – 7.7 pKi 8-9
pKi 7.5 – 7.7 [8-9]
15(S)-15-methyl-PGD2 Hs Full agonist 7.5 pKi 19
pKi 7.5 [19]
PGD2 Mm Full agonist 7.4 – 7.5 pKi 8-9
pKi 7.4 – 7.5 [8-9]
PGD3 Mm Full agonist 7.4 pKi 9
pKi 7.4 [9]
L-888,291 Hs Full agonist 7.3 pKi 7
pKi 7.3 (Ki 4.8x10-8 M) [7]
PGJ2 Mm Full agonist 7.3 pKi 9
pKi 7.3 [9]
15-deoxy-Δ12,14-PGD2 Mm Full agonist 7.3 pKi 9
pKi 7.3 [9]
indomethacin Hs Full agonist 6.1 – 7.7 pKi 19,22
pKi 6.1 – 7.7 [19,22]
Δ12-PGJ2 Mm Full agonist 6.4 pKi 9
pKi 6.4 [9]
PGF Hs Full agonist 6.4 pKi 19
pKi 6.4 [19]
13,14-dihydro-15-keto-PGF Hs Full agonist 6.3 pKi 19
pKi 6.3 [19]
PGF Mm Full agonist 6.2 pKi 9
pKi 6.2 [9]
indomethacin Mm Full agonist 5.7 – 6.0 pKi 8-9
pKi 5.7 – 6.0 [8-9]
PGE2 Mm Full agonist 5.5 pKi 9
pKi 5.5 [9]
U46619 Hs Full agonist 5.5 pKi 19
pKi 5.5 [19]
PGE2 Hs Full agonist 5.3 pKi 19
pKi 5.3 [19]
PGD2 Rn Full agonist 8.2 pIC50 20
pIC50 8.2 [20]
View species-specific agonist tables
Agonist Comments
13,14-dihydro-15-oxo-PGD2 and 15R-15-methyl-PGD2 are selective DP2 agonists [9,14]. The COX-1/2 inhibitor indomethacin [10] and the thromboxane metabolite 11-dehydro TXB2 [2] are low-potency DP2 agonists.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
fevipiprant Hs Antagonist 9.0 pKd 23-24
pKd 9.0 (Kd 1.02x10-9 M) [23-24]
[3H]ramatroban Hs Antagonist 8.1 pKd 22
pKd 8.1 [22]
QAV680 Hs Antagonist 7.8 pKd 23
pKd 7.8 (Kd 1.51x10-8 M) [23]
CAY 10471 Hs Antagonist 9.2 pKi 25
pKi 9.2 (Ki 6x10-10 M) [25]
OC000459 Rn Antagonist 8.5 pKi 16
pKi 8.5 (Ki 3x10-9 M) [16]
Description: Displacement of [3H]PGD2 from rat recombinant DP2
compound 51 (Crosignani et al., 2011) Hs Antagonist 8.2 pKi 4
pKi 8.2 (Ki 6.9x10-9 M) [4]
OC000459 Hs Antagonist 7.9 pKi 16
pKi 7.9 (Ki 1.3x10-8 M) [16]
Description: Displacement of [3H]PGD2 from human recombinant DP2
ramatroban Hs Antagonist 7.4 pKi 22
pKi 7.4 [22]
ramatroban Mm Antagonist 7.3 pKi 8
pKi 7.3 [8]
CAY 10471 Hs Antagonist 8.9 pIC50 17,25
pIC50 8.9 (IC50 1.2x10-9 M) [17,25]
AZD1981 Hs Antagonist 8.4 pIC50 11
pIC50 8.4 (IC50 4.3x10-9 M) [11]
Description: Displacement of [3H]PGD2 from human CRTH2 receptor
ramatroban Rn Antagonist 7.3 pIC50 20
pIC50 7.3 [20]
View species-specific antagonist tables
Antagonist Comments
The TP receptor antagonist ramatroban also blocks the DP2 receptor [21].

For a review on the use of DP2 antagonists to treat allergic inflammation see [12].
OC000459 antagonises [3H]PGD2 binding to native DP2 receptors in human Th2 lymphocytes with a Ki of 4nM [16].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  9,19
Tissue Distribution
Eosinophils.
Species:  Human
Technique:  RT-PCR, Southern blotting and in situ hybridisation.
References:  6
Stomach, small intestine, heart, thymus > colon, spinal cord, peripheral blood > brain, skeletal muscle, spleen.
Species:  Human
Technique:  Northern blotting.
References:  19
Eosinophils.
Species:  Human
Technique:  in situ hybridisation.
References:  19
Th2-type lymphocytes.
Species:  Human
Technique:  Northern blotting.
References:  15
Liver, lung, kidney, brain, heart, thymus, spleen, Th1 and Th2 cells.
Species:  Mouse
Technique:  RT-PCR.
References:  1
Lung, brain, ovary, spleen.
Species:  Rat
Technique:  RT-PCR.
References:  20
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 Assays
Measurement of Ca2+ levels in L1.2 cells transfected with the rat DP2 receptor.
Species:  Rat
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  20
Measurement of Ca2+ levels in L1.2 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  20
Measurement of cAMP levels in HEK 293 cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  19
Measurement of cAMP levels in ER293 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  ER293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  9
Measurement of cell migration of ER293 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  ER293 cells.
Response measured:  Induction of chemotaxis via a PI3 kinase-dependent pathway.
References:  9
Measurement of Ca2+ levels in K562 cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  K562 cells.
Response measured:  Ca2+ mobilisation.
References:  10
Measurement of Ca2+ mobilisation in human Th2 cells endogenously expressing the DP2 receptor.
Species:  Human
Tissue:  Th2 cells.
Response measured:  Ca2+ mobilisation.
References:  5,10
Measurement of cell migration of Jurkat cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Induction of chemotaxis.
References:  10
Measurement of cell migration of human Th2 cells, basophils and eosinophils endogenously expressing the DP2 receptor.
Species:  Human
Tissue:  Th2 cells, basophils, eosinophils.
Response measured:  Induction of chemotaxis.
References:  10
Physiological Functions
Eosinophil activation, chemotaxis and degranulation.
Species:  Human
Tissue:  Eosinophils.
References:  6
Stimulation of cytokine production.
Species:  Human
Tissue:  Th2 cells.
References:  26
Eosinophil activation.
Species:  Human
Tissue:  Eosinophils.
References:  5
Physiological Consequences of Altering Gene Expression
DP2 receptor knockout mice exhibit decreased cutaneous inflammatory responses. Reduced lymphocyte, eosinophil and basophil infiltration is observed along with a decrease in RANTES production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  18
In an allergic inflammatory model of asthma, DP2 knockout mice show enhanced eosinophil recruitment into the lung compared with wild-type littermate mice.
Species:  Human
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  3
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0008721 abnormal chemokine level PMID: 16888024 
Gpr44tm1Byl Gpr44tm1Byl/Gpr44tm1Byl
involves: C57BL/6J
MGI:1330275  MP:0003009 abnormal cytokine secretion PMID: 16081770 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0001845 abnormal inflammatory response PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0002492 decreased IgE level PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0001876 decreased inflammatory response PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0009815 decreased prostaglandin level PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44
MGI:1330275  MP:0005616 decreased susceptibility to type IV hypersensitivity reaction PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
involves: 129/Sv * BALB/c
MGI:1330275  MP:0008723 impaired eosinophil recruitment PMID: 18097056 
Gpr44tm1Byl Gpr44tm1Byl/Gpr44tm1Byl
involves: C57BL/6J
MGI:1330275  MP:0005011 increased eosinophil cell number PMID: 16081770 

References

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1. Abe H, Takeshita T, Nagata K, Arita T, Endo Y, Fujita T, Takayama H, Kubo M, Sugamura K. (1999) Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family. Gene227: 71-77. [PMID:9931443]

2. Böhm E, Sturm GJ, Weiglhofer I, Sandig H, Shichijo M, McNamee A, Pease JE, Kollroser M, Peskar BA, Heinemann A. (2004) 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. J Biol Chem279: 7663-7670. [PMID:14668348]

3. Chevalier E, Stock J, Fisher T, Dupont M, Fric M, Fargeau H, Leport M, Soler S, Fabien S, Pruniaux MP, Fink M, Bertrand CP, McNeish J, Li B. (2005) Cutting edge: chemoattractant receptor-homologous molecule expressed on Th2 cells plays a restricting role on IL-5 production and eosinophil recruitment. J Immunol175: 2056-2060. [PMID:16081770]

4. Crosignani S, Jorand-Lebrun C, Campbell G, Pretre A, Grippi-Vallotton, T, Quattropani, A, Bouscary-Desforges G, Bombrun A, Missotten, M, Humbert Y et al.. (2011) Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids. ACS Med Chem Lett2: 938-942.

5. Gazi L, Gyles S, Rose J, Lees S, Allan C, Xue L, Jassal R, Speight G, Gamble V, Pettipher R. (2005) Delta12-prostaglandin D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes. Prostaglandins Other Lipid Mediat75: 153-167. [PMID:15789622]

6. Gervais FG, Cruz RP, Chateauneuf A, Gale S, Sawyer N, Nantel F, Metters KM, O'Neill GP. (2001) Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. J Allergy Clin Immunol108: 982-988. [PMID:11742277]

7. Gervais FG, Morello JP, Beaulieu C, Sawyer N, Denis D, Greig G, Malebranche AD, O'Neill GP. (2005) Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol67: 1834-1839. [PMID:15755909]

8. Hata AN, Lybrand TP, Breyer RM. (2005) Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J Biol Chem280: 32442-32451. [PMID:16030019]

9. Hata AN, Zent R, Breyer MD, Breyer RM. (2003) Expression and molecular pharmacology of the mouse CRTH2 receptor. J Pharmacol Exp Ther306: 463-470. [PMID:12721327]

10. Hirai H, Tanaka K, Takano S, Ichimasa M, Nakamura M, Nagata K. (2002) Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. J Immunol168: 981-985. [PMID:11801628]

11. Luker T, Bonnert R, Brough S, Cook AR, Dickinson MR, Dougall I, Logan C, Mohammed RT, Paine S, Sanganee HJ et al.. (2011) Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. Bioorg. Med. Chem. Lett.21 (21): 6288-92. [PMID:21944852]

12. Ly TW, Bacon KB. (2005) Small-molecule CRTH2 antagonists for the treatment of allergic inflammation: an overview. Expert Opin Investig Drugs14: 769-773. [PMID:16022566]

13. Mathiesen JM, Christopoulos A, Ulven T, Royer JF, Campillo M, Heinemann A, Pardo L, Kostenis E. (2006) On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2. Mol Pharmacol69: 1441-1453. [PMID:16418339]

14. Monneret G, Cossette C, Gravel S, Rokach J, Powell WS. (2003) 15R-methyl-prostaglandin D2 is a potent and selective CRTH2/DP2 receptor agonist in human eosinophils. J Pharmacol Exp Ther304: 349-355. [PMID:12490611]

15. Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, Abe H, Tada K, Nakamura M, Sugamura K, Takano S. (1999) Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol162: 1278-1286. [PMID:9973380]

16. Pettipher R, Vinall SL, Xue L, Speight G, Townsend ER, Gazi L, Whelan CJ, Armer RE, Payton MA, Hunter MG. (2012) Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils. J. Pharmacol. Exp. Ther.340 (2): 473-82. [PMID:22106101]

17. Royer JF, Schratl P, Lorenz S, Kostenis E, Ulven T, Schuligoi R, Peskar BA, Heinemann A. (2007) A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. Allergy62 (12): 1401-9. [PMID:17714552]

18. Satoh T, Moroi R, Aritake K, Urade Y, Kanai Y, Sumi K, Yokozeki H, Hirai H, Nagata K, Hara T, Utsuyama M, Hirokawa K, Sugamura K, Nishioka K, Nakamura M. (2006) Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. J Immunol177: 2621-2629. [PMID:16888024]

19. Sawyer N, Cauchon E, Chateauneuf A, Cruz RP, Nicholson DW, Metters KM, O'Neill GP, Gervais FG. (2002) Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Br J Pharmacol137: 1163-1172. [PMID:12466225]

20. Shichijo M, Sugimoto H, Nagao K, Inbe H, Encinas JA, Takeshita K, Bacon KB, Gantner F. (2003) Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats. J Pharmacol Exp Ther307: 518-525. [PMID:12975488]

21. Sugimoto H, Shichijo M, Iino T, Manabe Y, Watanabe A, Shimazaki M, Gantner F, Bacon KB. (2003) An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro. J Pharmacol Exp Ther305: 347-352. [PMID:12649388]

22. Sugimoto H, Shichijo M, Okano M, Bacon KB. (2005) CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Delta12, 14-PGJ2- and indomethacin-induced agonist responses. Eur J Pharmacol524: 30-37. [PMID:16256979]

23. Sykes D, Bradley M, Riddy D, Willard L, Powell-Herlaar E, Sandham D, Watson S, Bauer C, Dubois G, Charlton S. (2014) QAW039, a slowly dissociating CRTh2 antagonist with potential for improved clinical efficacy. Eur. Respir. J.44 (Supl 58): 4074.

24. Sykes DA, Bradley ME, Riddy DM, Willard E, Reilly J, Miah A, Bauer C, Watson SJ, Sandham DA, Dubois G et al.. (2016) Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy. Mol. Pharmacol.89 (5): 593-605. [PMID:26916831]

25. Ulven T, Kostenis E. (2005) Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist. J Med Chem48: 897-900. [PMID:15715457]

26. Xue L, Gyles SL, Wettey FR, Gazi L, Townsend E, Hunter MG, Pettipher R. (2005) Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol175: 6531-6536. [PMID:16272307]

Contributors

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How to cite this page

David F. Woodward, Robert L. Jones, Mark Giembycz, Shuh Narumiya, Xavier Norel, Robert A. Coleman, Mark Abramovitz, Richard M. Breyer, Rebecca Hills.
Prostanoid receptors: DP2 receptor. Last modified on 22/02/2017. Accessed on 24/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=339.