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PTGDR  -  prostaglandin D2 receptor (DP)

Homo sapiens

Synonyms: AS1, ASRT1, DP, DP1, PGD receptor, ...
 
 
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Disease relevance of PTGDR

 

High impact information on PTGDR

  • We report that circulated human CD4+ T cells expressing the prostaglandin D2 receptor (CRTH2) are TH2 central memory T cells, characterized by their phenotype, TH2 cytokine production, gene-expression profile, and the ability to respond to allergens [6].
  • Further, we found that recombinant UG blocks DP-mediated nuclear factor-kappaB activation and suppresses COX-2 gene expression [7].
  • However, proinflammatory functions of PGD2 cannot be explained by DP alone [8].
  • Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP) [8].
  • In recent years, considerable progress has been made in unraveling the control mechanisms operating on the plant cell cycle and most of the key regulators have now been identified, including cyclin-dependent kinases (CDKs), cyclins, CDK-inhibitory proteins, the WEE kinase and proteins of the retinoblastoma-related protein (RBR)/E2F/DP pathway [9].
 

Chemical compound and disease context of PTGDR

 

Biological context of PTGDR

 

Anatomical context of PTGDR

  • Prostaglandin E2 and BW 245C (a synthetic DP receptor agonist) decreased OPG in the supernatants of human osteoblasts but not in immortalized cell lines [1].
  • Finally, we demonstrate that BW245C, but not DK-PGD(2), can delay the onset of apoptosis in cultured eosinophils, presumably through interaction with DP [18].
  • In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium [19].
  • PGD(2) and the highly selective DP-specific agonist L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)), but not PGE(2) competed for [(3)H]-PGD(2)-specific binding to LS174T cell membranes (K:(i) values of 0.4 nM and 7 nM, respectively) [3].
  • In this study, we examined the role of PGD(2) and DP receptors in regulating human penile smooth muscle contractility [20].
 

Associations of PTGDR with chemical compounds

 

Physical interactions of PTGDR

  • Prostaglandin D(2) (PGD(2)) binds to specific G-protein coupled receptors (DP) and induces smooth muscle relaxation by stimulating the synthesis of intracellular cAMP [20].
 

Regulatory relationships of PTGDR

  • Characterization of DP receptor null mice in which antigen-induced airway and inflammatory responses are attenuated and identification of CRTH2 as a novel PGD(2) receptor have shed light on the role of PGD(2) in the immune and inflammatory responses [22].
 

Other interactions of PTGDR

  • This revealed that the affinity of PGD(2) for CRTH2 is eight times less than its affinity for the DP receptor [23].
  • These effects were concentration-dependent and were inhibited by EP4 and DP receptor antagonists [1].
  • The hDP receptor consists of 359 amino acid residues with a predicted molecular mass of 40,276 and has the putative heptahelical transmembrane domains characteristics of G-protein-coupled receptors [17].
  • First, we show that PGD(2) exerts in vitro chemotactic effects on monocytes via CRTH2 activation while it inhibits the chemokine-driven migration of monocyte-derived DC through DP [24].
  • Additional to DP receptors, the PGD(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) binds the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPARgamma association [25].
 

Analytical, diagnostic and therapeutic context of PTGDR

References

  1. Implication of prostaglandin receptors in the accumulation of osteoprotegerin in human osteoblast cultures. Moreau, M., Boileau, C., Martel-Pelletier, J., Brunet, J., Laufer, S., Pelletier, J.P. J. Rheumatol. (2006) [Pubmed]
  2. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. Iwasaki, M., Nagata, K., Takano, S., Takahashi, K., Ishii, N., Ikezawa, Z. J. Invest. Dermatol. (2002) [Pubmed]
  3. The human prostanoid DP receptor stimulates mucin secretion in LS174T cells. Wright, D.H., Ford-Hutchinson, A.W., Chadee, K., Metters, K.M. Br. J. Pharmacol. (2000) [Pubmed]
  4. Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders. Cooper, B., Ahern, D. J. Clin. Invest. (1979) [Pubmed]
  5. HLA-linked susceptibility and resistance genes in Crohn's disease. Nakajima, A., Matsuhashi, N., Kodama, T., Yazaki, Y., Takazoe, M., Kimura, A. Gastroenterology (1995) [Pubmed]
  6. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Wang, Y.H., Ito, T., Wang, Y.H., Homey, B., Watanabe, N., Martin, R., Barnes, C.J., McIntyre, B.W., Gilliet, M., Kumar, R., Yao, Z., Liu, Y.J. Immunity (2006) [Pubmed]
  7. Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions. Mandal, A.K., Zhang, Z., Ray, R., Choi, M.S., Chowdhury, B., Pattabiraman, N., Mukherjee, A.B. J. Exp. Med. (2004) [Pubmed]
  8. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. Hirai, H., Tanaka, K., Yoshie, O., Ogawa, K., Kenmotsu, K., Takamori, Y., Ichimasa, M., Sugamura, K., Nakamura, M., Takano, S., Nagata, K. J. Exp. Med. (2001) [Pubmed]
  9. Green light for the cell cycle. Inzé, D. EMBO J. (2005) [Pubmed]
  10. D-penicillamine-induced polymyositis in patients with rheumatoid arthritis. Takahashi, K., Ogita, T., Okudaira, H., Yoshinoya, S., Yoshizawa, H., Miyamoto, T. Arthritis Rheum. (1986) [Pubmed]
  11. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Felson, D.T., Anderson, J.J., Meenan, R.F. Arthritis Rheum. (1990) [Pubmed]
  12. Messenger RNA expression profiling of genes involved in epidermal growth factor receptor signalling in human cancer cells treated with scanning array-designed antisense oligonucleotides. Petch, A.K., Sohail, M., Hughes, M.D., Benter, I., Darling, J., Southern, E.M., Akhtar, S. Biochem. Pharmacol. (2003) [Pubmed]
  13. Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew). Kan, K.K., Jones, R.L., Ngan, M.P., Rudd, J.A. Eur. J. Pharmacol. (2003) [Pubmed]
  14. Effects of prostaglandin D2 on helper T cell functions. Tanaka, K., Hirai, H., Takano, S., Nakamura, M., Nagata, K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. Role of prostanoid DP receptor variants in susceptibility to asthma. Oguma, T., Palmer, L.J., Birben, E., Sonna, L.A., Asano, K., Lilly, C.M. N. Engl. J. Med. (2004) [Pubmed]
  16. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Cheng, K., Wu, T.J., Wu, K.K., Sturino, C., Metters, K., Gottesdiener, K., Wright, S.D., Wang, Z., O'neill, G., Lai, E., Waters, M.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Molecular cloning and characterization of the human prostanoid DP receptor. Boie, Y., Sawyer, N., Slipetz, D.M., Metters, K.M., Abramovitz, M. J. Biol. Chem. (1995) [Pubmed]
  18. Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. Gervais, F.G., Cruz, R.P., Chateauneuf, A., Gale, S., Sawyer, N., Nantel, F., Metters, K.M., O'neill, G.P. J. Allergy Clin. Immunol. (2001) [Pubmed]
  19. In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium. Senior, J., Sangha, R., Baxter, G.S., Marshall, K., Clayton, J.K. Br. J. Pharmacol. (1992) [Pubmed]
  20. Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle. Moreland, R.B., Nehra, A., Kim, N.N., Min, K.S., Albadawi, H., Watkins, M.T., Goldstein, I., Traish, A.M. Int. J. Impot. Res. (2002) [Pubmed]
  21. New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes. Noguchi, E., Shibasaki, M., Kamioka, M., Yokouchi, Y., Yamakawa-Kobayashi, K., Hamaguchi, H., Matsui, A., Arinami, T. Clin. Exp. Allergy (2002) [Pubmed]
  22. Hematopoietic prostaglandin D synthase. Kanaoka, Y., Urade, Y. Prostaglandins Leukot. Essent. Fatty Acids (2003) [Pubmed]
  23. Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Sawyer, N., Cauchon, E., Chateauneuf, A., Cruz, R.P., Nicholson, D.W., Metters, K.M., O'Neill, G.P., Gervais, F.G. Br. J. Pharmacol. (2002) [Pubmed]
  24. Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells. Gosset, P., Bureau, F., Angeli, V., Pichavant, M., Faveeuw, C., Tonnel, A.B., Trottein, F. J. Immunol. (2003) [Pubmed]
  25. Positioning prostanoids of the D and J series in the immunopathogenic scheme. Herlong, J.L., Scott, T.R. Immunol. Lett. (2006) [Pubmed]
  26. Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa. Nantel, F., Fong, C., Lamontagne, S., Wright, D.H., Giaid, A., Desrosiers, M., Metters, K.M., O'Neill, G.P., Gervais, F.G. Prostaglandins Other Lipid Mediat. (2004) [Pubmed]
 
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