Prostaglandin D 2 receptor , type 2 ( Eng. Prostaglandin D 2 receptor 2 ; PTGDR2), or G protein-coupled receptor, 44 (( G Protein-Coupled Receptor 44 ; GPR44) - a protein of the G-coupled receptor family -protein , human product of the PTGDR2 gene [1] . It belongs to the group of prastaglandin receptors and prostaglandin D 2 binds to PTGDR1 . Activation of the receptor by prostaglandin D 2 or other ligands is associated with certain physiological and pathological reactions, mainly associated with allergies, inflammation and some diseases person.
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| , CD294, CRTH2, DL1R, DP2, GPR44, prostaglandin D2 receptor 2 | |||||||||||||
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Content
Gene
The PTGDR1 gene is located on chromosome 14 at the chromosomal locus (position 14q22.1) associated with the development of asthma and other allergic disorders. [2] PTGDR1 consists of 4 introns and 5 exons, encodes a protein of about 44 kDa. As a result of alternative splicing, several transcriptional variants are formed.
Expression
The receptor is expressed on several types of cells involved in the mediation of allergic and inflammatory reactions. it is expressed by mast cells , basophils and eosinophils , Th2 cells and dendritic cells , as well as epithelial cells of the respiratory tract , endothelial vascular cells, mucus producing goblet cells of the nasal tract and colon and nasal serous glands. [3] [4] In addition, in the mouse, the GPR44 protein is expressed in the placenta and testes [5] , and mRNA was also detected in some parts of the brain. [6] [7]
Ligands
PGD2 binds and activates the receptor at concentrations from 0.5 to 1 nM. According to the potency of activating the receptor, prostaglandins are arranged in the following order: PGD2 >> PGE2> prostaglandin F2 alpha> PGI2 = trobaxan A2, and PGD2 is 100 times more powerful receptor activator than the next PGE2.
Cell Activation Mechanism
In humans, there are 8 prostanoid receptors. GPR44 refers to relaxing prostanoid receptors, which act through the activation of the Gsα subunit , which, in turn, increases the cellular level of cAMP and initiates cAMP-dependent signaling pathways that regulate cellular functions. [3] [8] Activation of the receptor also causes mobilization of calcium. On the other hand, the ligand-activated receptor GPR44 mobilizes GRK kinase 2 (BARK1) and arrestin 2 (ARRB1). These paths disconnect the receptor from G-proteins and lead to its internalization, which limits the lifetime of the receptor and, therefore, causes its desensitization [9] .
Notes
- ↑ Entrez Gene: GPR44 G protein-coupled receptor 44 .
- ↑ Lee YH, Choi SJ, Ji JD, Song GG PTGDR polymorphisms and susceptibility to asthma: a meta-analysis (Eng.) // Molecular Biology Reports : journal. - 2013 .-- Vol. 40 , no. 3 . - P. 2195-2203 . - DOI : 10.1007 / s11033-012-2280-x . - PMID 23192614 .
- ↑ 1 2 Matsuoka T., Narumiya S. Prostaglandin receptor signaling in disease (English) // The Scientific World Journal : journal. - 2007. - Vol. 7 . - P. 1329-1347 . - DOI : 10.1100 / tsw.2007.182 . - PMID 17767353 .
- ↑ Claar D., Hartert TV, Peebles RS The role of prostaglandins in allergic lung inflammation and asthma (Eng.) // Expert Review of Respiratory Medicine : journal. - 2015. - Vol. 9 , no. 1 . - P. 55-72 . - DOI : 10.1586 / 17476348.2015.992783 . - PMID 25541289 .
- ↑ Rossitto M., Ujjan S., Poulat F., Boizet-Bonhoure B. Multiple roles of the prostaglandin D2 signaling pathway in reproduction (Eng.) // Reproduction (Cambridge, England): journal. - 2015. - Vol. 149 , no. 1 . - P. R49-58 . - DOI : 10.1530 / REP-14-0381 . - PMID 25269616 .
- ↑ Yagami T., Koma H., Yamamoto Y. Pathophysiological Roles of Cyclooxygenases and Prostaglandins in the Central Nervous System (Eng.) // Molecular Neurobiology: journal. - 2016. - Vol. 53 , no. 7 . - P. 4754-4771 . - DOI : 10.1007 / s12035-015-9355-3 . - PMID 26328537 .
- ↑ Boie Y., Sawyer N., Slipetz DM, Metters KM, Abramovitz M. Molecular cloning and characterization of the human prostanoid DP receptor (Eng.) // The Journal of Biological Chemistry : journal. - 1995. - Vol. 270 , no. 32 . - P. 18910-18916 . - DOI : 10.1074 / jbc.270.32.18910 . - PMID 7642548 .
- ↑ Kobeissy FH, Doré S., Shafique Ahmad A. Cytoprotective Role of Prostaglandin D2 DP1 Receptor against Neuronal Injury Following Acute Excitotoxicity and Cerebral Ischemia. (English) : journal. - PMID 26269890 .
- ↑ Korbecki J., Baranowska-Bosiacka I., Gutowska I., Chlubek D. Cyclooxygenase pathways (neopr.) // Acta Biochimica Polonica. - 2014.- T. 61 , No. 4 . - S. 639-649 . - PMID 25343148 .
Literature
- Boyce JA The role of mast cells in asthma (neopr.) // Prostaglandins Leukot. Essent. Fatty Acids - 2004. - T. 69 , No. 2-3 . - S. 195-205 . - DOI : 10.1016 / S0952-3278 (03) 00081-4 . - PMID 12895603 .
- Chiba T., Kanda A., Ueki S., etal. Possible novel receptor for PGD2 on human bronchial epithelial cells (English) // Int. Arch. Allergy Immunol. : journal. - 2007. - Vol. 143 Suppl 1 . - P. 23-7 . - DOI : 10.1159 / 000101400 . - PMID 17541272 .
- Senior J., Sangha R., Baxter GS, etal. In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium (English) // Br. J. Pharmacol. : journal. - 1992. - Vol. 107 , no. 1 . - P. 215-221 . - DOI : 10.1111 / j.1476-5381.1992.tb14489.x . - PMID 1422574 .
- Boie Y., Sawyer N., Slipetz DM, etal. Molecular cloning and characterization of the human prostanoid DP receptor (Eng.) // J. Biol. Chem. : journal. - 1995. - Vol. 270 , no. 32 . - P. 18910-18916 . - DOI : 10.1074 / jbc.270.32.18910 . - PMID 7642548 .
- Ishikawa TO, Tamai Y., Rochelle JM, etal. Mapping of the genes encoding mouse prostaglandin D, E, and F and prostacyclin receptors (Eng.) // Genomics : journal. - Academic Press , 1997. - Vol. 32 , no. 2 . - P. 285-288 . - DOI : 10.1006 / geno.1996.0118 . - PMID 8833158 .
- Kobayashi T., Ushikubi F., Narumiya S. Amino acid residues conferring ligand binding properties of prostaglandin I and prostaglandin D receptors. Identification by site-directed mutagenesis // J. Biol. Chem. : journal. - 2000. - Vol. 275 , no. 32 . - P. 24294-24303 . - DOI : 10.1074 / jbc.M002437200 . - PMID 10827082 .
- Wright DH, Ford-Hutchinson AW, Chadee K., Metters KM The human prostanoid DP receptor stimulates mucin secretion in LS174T cells (Eng.) // Br. J. Pharmacol. : journal. - 2001. - Vol. 131 , no. 8 . - P. 1537-1545 . - DOI : 10.1038 / sj.bjp.0703688 . - PMID 11139429 .
- Gervais FG, Cruz RP, Chateauneuf A., etal. Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP (English) // J. Allergy Clin. Immunol. : journal. - 2002. - Vol. 108 , no. 6 . - P. 982-988 . - DOI : 10.1067 / mai.2001.119919 . - PMID 11742277 .
- Noguchi E., Shibasaki M., Kamioka M., etal. New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes (English) // Clin. Exp. Allergy : journal. - 2002. - Vol. 32 , no. 1 . - P. 93-6 . - DOI : 10.1046 / j.0022-0477.2001.01261.x . - PMID 12002745 .
- Hakonarson H., Bjornsdottir US, Halapi E., etal. A Major Susceptibility Gene for Asthma Maps to Chromosome 14q24 (Eng.) // Am. J. Hum. Genet. : journal. - 2002. - Vol. 71 , no. 3 . - P. 483-491 . - DOI : 10.1086 / 342205 . - PMID 12119603 .
- Iwasaki M., Nagata K., Takano S., etal. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis (Eng.) // J. Invest. Dermatol. : journal. - 2002. - Vol. 119 , no. 3 . - P. 609-616 . - DOI : 10.1046 / j.1523-1747.2002.01862.x . - PMID 12230502 .
- Strausberg RL, Feingold EA, Grouse LH, etal. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences (Eng.) // Proceedings of the National Academy of Sciences of the United States of America : journal. - 2003. - Vol. 99 , no. 26 . - P. 16899-16903 . - DOI : 10.1073 / pnas.242603899 . - PMID 12477932 .
- Moreland RB, Nehra A., Kim NN, etal. Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle (English) // Int. J. Impot. Res. : journal. - 2003. - Vol. 14 , no. 6 . - P. 446–452 . - DOI : 10.1038 / sj.ijir.3900900 . - PMID 12494276 .
- Faveeuw C., Gosset P., Bureau F., etal. Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways (English) // Eur. J. Immunol. : journal. - 2003. - Vol. 33 , no. 4 . - P. 889-898 . - DOI : 10.1002 / eji.200323330 . - PMID 12672054 .
- Angeli V., Staumont D., Charbonnier AS, etal. Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses (Eng.) // J. Immunol. : journal. - 2004. - Vol. 172 , no. 6 . - P. 3822-3829 . - DOI : 10.4049 / jimmunol . 17.6.6.3822 . - PMID 15004188 .
- Gerhard DS, Wagner L., Feingold EA, etal. The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) (Eng.) // Genome Res. : journal. - 2004. - Vol. 14 , no. 10B . - P. 2121-2127 . - DOI : 10.1101 / gr.2596504 . - PMID 15489334 .
- Oguma T., Palmer LJ, Birben E., etal. Role of prostanoid DP receptor variants in susceptibility to asthma (Eng.) // N. Engl. J. Med. : journal. - 2004. - Vol. 351 , no. 17 . - P. 1752-1763 . - DOI : 10.1056 / NEJMoa031785 . - PMID 15496624 .
- Spik I., Brénuchon C., Angéli V., etal. Activation of the prostaglandin D2 receptor DP2 / CRTH2 increases allergic inflammation in mouse (Eng.) // J. Immunol. : journal. - 2005. - Vol. 174 , no. 6 . - P. 3703-3708 . - DOI : 10.4049 / jimmunol . 174.6.3703 . - PMID 15749909 .
- Hirano Y., Shichijo M., Deguchi M., etal. Synergistic effect of PGD2 via prostanoid DP receptor on TNF-alpha-induced production of MCP-1 and IL-8 in human monocytic THP-1 cells (Eng.) // Eur. J. Pharmacol. : journal. - 2007. - Vol. 560 , no. 1 . - P. 81-8 . - DOI : 10.1016 / j.ejphar.2007.01.01.003 . - PMID 17307163 .