Prostaglandin D₂

Prostaglandin D₂ (PGD₂) is the major eicosanoid product of mast cells and is released in large quantities during allergic and asthmatic anaphylaxis.¹ Mastocytosis patients produce excessive amounts of PGD₂, which causes vasodilation, flushing, hypotension, and syncopal episodes.¹ PGD₂ is also produced in the brain via an alternative pathway involving a soluble, secreted PGD-synthase also known as β-trace.^2,3 In the brain, PGD₂ produces normal physiological sleep and lowering of body temperature.^2,3 Further pharmacological actions include inhibition of platelet aggregation and relaxation of vascular smooth muscle.⁴ PGD₂ inhibits human ovarian tumor cell proliferation with an IC₅₀ of 6.8 µM.⁵

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1. Roberts, L.J., II, and Sweetman, B.J. Metabolic fate of endogenously synthesized prostaglandin D₂ in a human female with mastocytosis. Prostaglandins 30(3), 383-400 (1985).

2. Hayaishi, O. Sleep-wake regulation by prostaglandins D₂ and E₂. The Journal of Biological Chemisty 263(29), 14593-14596 (1988).

3. Onoe, H., Ueno, R., Fujita, I., et al. Prostaglandin D₂, a cerebral sleep-inducing substance in monkeys. Proc. Natl. Acad. Sci. USA 85(11), 4082-4086 (1988).

4. Giles, H., and Leff, P. The biology and pharmacology of PGD₂. Prostaglandins 35(2), 277-300 (1988).

5. Kikuchi, Y., Kita, T., Hirata, J., et al. Preclinical studies of antitumor prostaglandins by using human ovarian cancer cells. Cancer Metastasis Rev. 13(3-4), 309-315 (1994).

Wu, Z., Xiao, H., Rao, D., et al. Analytical strategy for oxylipin annotation by combining chemical derivatization-based retention index algorithm and feature tandem mass spectrometric fragmentation as a biomarker discovery tool. Anal. Chem. 95(43), 15933-15942 (2023).

Pang, Y., Liu, X., Zhao, C., et al. LC-MS/MS-based arachidonic acid metabolomics in acute spinal cord injury reveals the upregulation of 5-LOX and COX-2 products. Free Radic. Biol. Med. 193(Pt 1), 363-372 (2022).

Archambault, A.-S., Brassard, J., Bernatchez, É., et al. Human and mouse eosinophils differ in their ability to biosynthesize eicosanoids, docosanoids, the endocannabinoid 2-arachidonoyl-glycerol and its congeners. Cells 11(1), 141 (2022).

Archambault, A.-S., Zaid, Y., Rakotoarivelo, V., et al. High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients. The FASEB Journal 35(6), e21666 (2021).

Roberts, L.M., Schwarz, B., Speranza, E., et al. Pulmonary infection induces persistent, pathogen-specific lipidomic changes influencing trained immunity. iScience 24(9), 103025 (2021).

Hartling, I., Cremonesi, A., Osuna, E., et al. Quantitative profiling of inflammatory and pro-resolving lipid mediators in human adolescents and mouse plasma using UHPLC-MS/MS. Clin. Chem. Lab. Med. 59(11), 1811-1823 (2021).

Oyesola, O.O., Duque, C., Huang, L.C., et al. The prostaglandin D₂ receptor CRTH2 promotes IL-33-induced ILC2 accumulation in the lung. J. Immunol. 204(4), 1001-1011 (2020).

Archambault, A.-S., Zaid, Y., Rakotoarivelo, V., et al. Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites. medRxiv (2020).

Brouwers, H., Jónasdóttir, H.S., Kuipers, M.E., et al. Anti-inflammatory and proresolving effects of the omega-6 polyunsaturated fatty acid adrenic acid. J. Immunol. 205(10), 2840-2849 (2020).

Meriwether, D., Sulaiman, D., Volpe, C., et al. Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model. J. Clin. Invest. 130, 3670-3685 (2019).

Schmidleithner, L., Thabet, Y., Schönfeld, E., et al. Enzymatic activity of HPGD in Treg cells suppresses Tconv cells to maintain adipose tissue homeostasis and prevent metabolic dysfunction. Immunity 50(5), 1232-1248 (2019).

Dalli, J., Colas, R.A., Walker, M.E., et al. Lipid Mediator Metabolomics via LC-MS/MS Profiling and Analysis. Clinical Metabolomics 59-72 (2018).

Sorgi, C.A., Peti, A.P.F., Petta, T., et al. Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays. Sci. Data 5, 180167 (2018).

Suganami, A., Fujino, H., Okura, I., et al. Human DP and EP₂ prostanoid receptors take on distinct forms depending on the diverse binding of different ligands. FEBS J. 283(21), 3931-3940 (2016).

Gouveia-Figueira, S., Karlsson, J., Deplano, A., et al. Characterisation of (R)-2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide as a dual fatty acid amide hydrolase: Cyclooxygenase inhibitor. PLoS One 10(9), e0139212 (2015).

Sasaki, A., Fukuda, H., Shiida, N., et al. Determination of ω-6 and ω-3 PUFA metabolites in human urine samples using UPLC/MS/MS. Anal. Bioanal. Chem. 407(6), 1625-1639 (2015).

Schröder, R., Xue, L., Konya, V., et al. PGH₁, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP₂. PLoS One 7(3), e33329 (2012).

Whittle, B.J., Silverstein, A.M., Mottola, D.M., et al. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: Treprostinil is a potent DP₁ and EP₂ agonist. Biochem. Pharmacol. 84(1), 68-75 (2012).

Qi, H.-Y., Daniels, M.P., Liu, Y., et al. A cytosolic phospholipase A₂-initiated lipid mediator pathway induces autophagy in macrophages. J. Immunol. 187(10), 5286-5292 (2011).

Woodward, D.F., Krauss, A.H.P., Chen, J., et al. Pharmacological characterization of a novel antiglaucoma agent, bimatoprost (AGN 192024). J. Pharmacol. Exp. Ther. 305(2), 772-785 (2003).

Waffo-Téguo, P., Hawthorne, M.E., Cuendet, M., et al. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutr. Cancer 40(2), 173-179 (2001).

Rao, C.V., Desai, D., Rivenson, A., et al. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res. 55(11), 2310-2315 (1995).