Prostaglandin DP1 receptor
PTGDR | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process |
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Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 14: 52.27 – 52.28 Mb | Chr 14: 45.09 – 45.1 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The prostaglandin D2 receptor 1 (DP1), a
Gene
The PTGDR1 gene is located on chromosome 14 at position q22.1, (i.e. 14q22.1), a chromosomal locus associated with asthma and other allergic disorders.
Expression
DP1 is expressed primarily by cells involved in mediating allergic and inflammatory reactions, i.e. human and rodent
Ligands
Activating ligands
PGD2 binds to and activates DP1 at concentrations in the 0.5 to 1
The drug treprostinil is a high affinity ligand for and potent activator of not only DP1 but also two other prostanoid receptors, EP2 and IP.[16]
Inhibiting ligands
Asapiprant (S-555739) and laropiprant are selective receptor antagonists of DP1 whereas vidupiprant is a receptor antagonist for both DP1 and DP2.[17]
Mechanisms of cell activation
Among the 8 human prostanoid receptors, DP1, along with
Activities
Allergy
Tissue studies
Studies in mouse as well as human tissues and cells find that DP1 stimulation has numerous pro-allergic effects. DP1 activation blocks the production of
Animal studies
Studies of experimentally-induced allergic responses in animals further implicate DP1 in allergy. DP1
Human studies
Allergen inhalation challenge of humans produces rises in the PGD2 levels in their bronchoalveolar lavage fluids. Furthermore, the administration of PGD2 into the nose or skin of human volunteers produces local symptoms of allergy and the inhalation of PGD2 into asthmatics causes constriction of the airways as well as the potentiation of airway constriction responses.[9] These reactions, similar to those produced in animal studies, may be mediated by DP1.
Central nervous system
PGD2 is the most abundant prostanoid in the brains of humans and other mammals and DP1 receptors are located on arachnoid mater trabecular cells in mouse basal forebrain. The PGD2-DP1 pathway is involved in the regulation of non-rapid eye movement sleep in rodents: infusion of PGD2 into the lateral ventricle of mice or the brain of rats induces an increase in the amount of non-rapid eye movement sleep in wild-type (WT) but not DP1-deficient animals. This sleep-induction appears to involve the DP1-dependent stimulation of adenosine formation and subsequent simulation of the adenosine A2A receptor by adenosine.[24][25] In humans, a genetic variant of ADA associated with the reduced metabolism of adenosine to inosine has been reported to deep sleep and SWA during sleep. These studies suggest that DP1 has a similar role in the sleep of humans.[25]
Pulmonary hypertension
Pulmonary arterial hypertension, Who group 1 (see Pulmonary hypertension#Causes), in humans in commonly treated with specific pulmonary artery vasodilators that increase survival such as the prostacyclin I2 (PGI2) mimetics including treprostinil, epoprostanol, iloprost, and beraprost. Recent studies find that DP1 as well as the PGI2 receptor protein are expressed in human pulmonary arteries and veins; that treprostinil but not iloprost caused pulmonary vein relaxation in part by acting through DP1 in insolated human pulmonary vascular preparations; and that the effect of treprostinil on DP1 in human pulmonary veins may contribute to its therapeutic efficacy in primary pulmonary hypertension.[26]
Reproduction
Studies in male mice indicate that DP1 activation induces the translocation of SOX9 into the nucleus thereby signaling for the maturation of Sertoli cells and embryonic gonads. Disruption of this DP1-activated circuit leads to disordered maturation of the male reproductive organs such as cryptorchidism (i.e. failure of testes descent into the scrotum) in mice and, it is suggested, may also do so in humans.[10]
Genomics studies
Human
See also
- Prostaglandin receptors
- Prostanoid receptors
- Prostaglandin DP2 receptor
- Eicosanoid receptor
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000168229 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000071489 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: PTGDR prostaglandin D2 receptor (DP)".
- ^ S2CID 2643718.
- ^ "PTGDR prostaglandin D2 receptor [Homo sapiens (Human)] - Gene - NCBI".
- ^ PMID 17767353.
- ^ PMID 25541289.
- ^ PMID 25269616.
- S2CID 11624385.
- ^ PMID 7642548.
- ^ "DP1 receptor | Prostanoid receptors | IUPHAR/BPS Guide to PHARMACOLOGY".
- ^ PMID 9579725.
- PMID 11301410.
- PMID 27286723.
- S2CID 19977989.
- PMID 26269890.
- ^ PMID 25343148.
- PMID 18946232.
- PMID 25179301.
- S2CID 34914925.
- PMID 21508345.
- S2CID 207058745.
- ^ PMID 25175972.
- PMID 23850788.
- PMID 25704194.
Further reading
- Boyce JA (2004). "The role of mast cells in asthma". Prostaglandins Leukot. Essent. Fatty Acids. 69 (2–3): 195–205. PMID 12895603.
- Chiba T, Kanda A, Ueki S, et al. (2007). "Possible novel receptor for PGD2 on human bronchial epithelial cells". Int. Arch. Allergy Immunol. 143 (Suppl 1): 23–7. S2CID 29630170.
- Senior J, Sangha R, Baxter GS, et al. (1992). "In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium". Br. J. Pharmacol. 107 (1): 215–21. PMID 1422574.
- Boie Y, Sawyer N, Slipetz DM, et al. (1995). "Molecular cloning and characterization of the human prostanoid DP receptor". J. Biol. Chem. 270 (32): 18910–6. PMID 7642548.
- Ishikawa TO, Tamai Y, Rochelle JM, et al. (1997). "Mapping of the genes encoding mouse prostaglandin D, E, and F and prostacyclin receptors". Genomics. 32 (2): 285–8. PMID 8833158.
- Kobayashi T, Ushikubi F, Narumiya S (2000). "Amino acid residues conferring ligand binding properties of prostaglandin I and prostaglandin D receptors. Identification by site-directed mutagenesis". J. Biol. Chem. 275 (32): 24294–303. PMID 10827082.
- Wright DH, Ford-Hutchinson AW, Chadee K, Metters KM (2001). "The human prostanoid DP receptor stimulates mucin secretion in LS174T cells". Br. J. Pharmacol. 131 (8): 1537–45. PMID 11139429.
- Gervais FG, Cruz RP, Chateauneuf A, et al. (2002). "Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP". J. Allergy Clin. Immunol. 108 (6): 982–8. PMID 11742277.
- Noguchi E, Shibasaki M, Kamioka M, et al. (2002). "New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes". Clin. Exp. Allergy. 32 (1): 93–6. S2CID 24779233.
- Hakonarson H, Bjornsdottir US, Halapi E, et al. (2002). "A Major Susceptibility Gene for Asthma Maps to Chromosome 14q24". Am. J. Hum. Genet. 71 (3): 483–91. PMID 12119603.
- Iwasaki M, Nagata K, Takano S, et al. (2002). "Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis". J. Invest. Dermatol. 119 (3): 609–16. PMID 12230502.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Moreland RB, Nehra A, Kim NN, et al. (2003). "Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle". Int. J. Impot. Res. 14 (6): 446–52. S2CID 25830532.
- Faveeuw C, Gosset P, Bureau F, et al. (2003). "Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways". Eur. J. Immunol. 33 (4): 889–98. S2CID 34871329.
- Angeli V, Staumont D, Charbonnier AS, et al. (2004). "Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses". J. Immunol. 172 (6): 3822–9. PMID 15004188.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. PMID 15489334.
- Oguma T, Palmer LJ, Birben E, et al. (2004). "Role of prostanoid DP receptor variants in susceptibility to asthma". N. Engl. J. Med. 351 (17): 1752–63. PMID 15496624.
- Spik I, Brénuchon C, Angéli V, et al. (2005). "Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse". J. Immunol. 174 (6): 3703–8. PMID 15749909.
- Hirano Y, Shichijo M, Deguchi M, et al. (2007). "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". Eur. J. Pharmacol. 560 (1): 81–8. PMID 17307163.
- Wong LY, Zheng J, Wilhelmsen K, Li K, Ortiz ME, Schnicker NJ, McCray PB, Perlman S (2022). "Eicosanoid signaling blockade protects middle-aged mice from severe COVID-19". Nature. 605 (7908): 146–151. PMID 33907749.
External links
- "Prostanoid Receptors: DP1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-09.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.