Disease relevance of PTGDR

• CONCLUSION: Our results show that activation of EP4 or DP receptors decreased the accumulation of OPG in supernatants of osteoblasts in culture, and suggest that these receptors could be interesting pharmacological targets in bone diseases [1].
• Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis [2].
• Selective high affinity ligands were used, therefore, to evaluate DP regulation of mucous secretion in LS174T human colonic adenocarcinoma cells [3].
• Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders [4].
• DP genes showed no significant association with Crohn's disease [5].

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

• Among 329 patients with rheumatoid arthritis treated with D-penicillamine (DP), we found 4 cases of polymyositis [10].
• We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA) [11].
• Phosphorothioate-modified 21-mer AS1 and AS2 ODNs inhibited the growth of an established human A431 cancer cell line as well as primary glioma cells from human subjects when delivered as cationic lipoplexes [12].
• The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent [13].
• Prostaglandin (PG) D(2) is abundantly produced by mast cells in the sites of allergic inflammations and acts on various cell types through its receptors DP and CRTH2 [14].

Biological context of PTGDR

• These define four common three-SNP haplotypes, which vary in their ability to support transcription of PTGDR and have distinct DNA-binding-protein affinity profiles [15].
• Individual PTGDR SNPs were significantly associated with asthma in both populations [15].
• The residual NA-induced vasodilation in male DP(-/-) mice was aspirin-sensitive [16].
• The signal transduction pathway of the cloned hDP receptor was studied by transfecting the hDP expression vector in HEK 293(EBNA) cells [17].
• Northern blot analysis of human tissue showed that the hDP receptor was a very discrete tissue distribution and was detectable only in retina and small intestine [17].

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

• Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans [16].
• It has been reported that mice lacking PGD receptor fail to develop the bronchial hyper-responsiveness upon ovalbumin challenge, suggesting that PGD2 functions as a mediator of allergic asthma [21].
• New polymorphisms of haematopoietic prostaglandin D synthase and human prostanoid DP receptor genes [21].
• Activation of the hDP receptor with PGD2 resulted in an elevation of intracellular cAMP and in mobilization of Ca2+, but did not lead to generation of inositol 1,4,5-trisphosphate [17].
• The activation of cyclic AMP production by PGD(2) and L-644,698, but not PGE(2), was inhibited by the selective DP antagonist BW A868C [3].

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

• METHODS: We identified and evaluated combinations of genetic variants that influence PTGDR transcription for disease association in case-control studies of 518 white patients with asthma and 175 white controls and 80 black patients with asthma and 45 black controls [15].
• Molecular cloning and characterization of the human prostanoid DP receptor [17].
• The expression of hDP in LS174T cells was confirmed at the mRNA level by reverse transcriptase-polymerase chain reaction, and at the protein level by radioligand binding assays and signal transduction (cyclic AMP accumulation) assays [3].
• This study demonstrates the localization of the prostaglandin (PG)D(2) receptor (DP) within the mucous-secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion [3].
• METHODS: DP mRNA expression was detected by in situ hybridization while PGDS, CRTH2 and various leukocyte markers expression were revealed by immunohistochemistry [26].

References