Prostaglandin D2

Prostaglandin D2

Names
IUPAC name 9α,15S-Dihydroxy-11-oxo-prosta-5Z,13E-dien-1-oic acid
Identifiers
CAS Number	41598-07-6  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15555  N
ChemSpider	395250  N
ECHA InfoCard	100.164.741
IUPHAR/BPS	1881 1891
KEGG	C00696  N
MeSH	Prostaglandin+D2
PubChem CID	448457
UNII	RXY07S6CZ2  Y
CompTox Dashboard (EPA)	DTXSID30897162
InChI InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-18,21-22H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,18-/m0/s1 N Key: BHMBVRSPMRCCGG-OUTUXVNYSA-N N InChI=1/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-18,21-22H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,18-/m0/s1 Key: BHMBVRSPMRCCGG-OUTUXVNYBP
SMILES CCCCC[C@@H](/C=C/[C@@H]1[C@H]([C@H](CC1=O)O)C/C=C\CCCC(=O)O)O
Properties
Chemical formula	C20H32O5
Molar mass	352.471 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

Prostaglandin D₂ (or PGD₂) is a prostaglandin that binds to the receptor PTGDR (DP₁), as well as CRTH2 (DP₂). ^{[1] [2]} It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amounts of PGD₂ are found only in the brain and in mast cells. It is critical to development of allergic diseases such as asthma. Research carried out in 1989 ^[3] found PGD₂ is the primary mediator of vasodilation (the "niacin flush") after ingestion of niacin (nicotinic acid).

A 2012 research paper indicates a causal link between elevated levels of localized PGD₂ and hair growth inhibition. ^[4] Applied topically, the researchers found PGD₂ prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD₂ had inhibited hair growth. The researchers also found PGD₂ levels were much higher in balding scalp tissue than nonbalding scalp tissue, through increased levels of prostaglandin D2 synthase. The paper suggested that inhibition of hair growth involved binding of PGD₂ to a DP₂ receptor, and that DP₂ therefore would be a therapeutic target for androgenic alopecia in both men and women with hair loss and thinning. ^[5] Because PGD₂'s relation to asthma has been known for several years, several drugs that seek to reduce the effect of PGD₂ through blocking the DP₂ are already in clinical trials. ^[5]

Production

• Cellular synthesis occurs through the arachidonic acid cascade with the final conversion from PGH₂ done by PGD₂ synthase (PTGDS).
• In the brain, production occurs via an alternative pathway through the soluble, secreted enzyme β-trace ^[6]

Effects

• PGD₂ promotes bronchoconstriction and vasoconstriction during times of Inflammation to alert the host of danger. Its concentration in asthma patients is 10 times higher than in control patients, especially after it is brought into contact with allergens, air pollution, secondhand smoke and smoke.
• PGD2 is involved in the regulation of reducing body temperature in sleep, and acts opposite to PGE₂.
• Elevated levels of PGD₂ and PGD₂ synthase in scalp hair follicles may be partially responsible for male pattern baldness. ^[7]
• PGD₂ also plays a part in male sexual development. It forms a feedforward loop with Sox9, which is activated by the SRY of the Y chromosome. PGD2, in a different feedforward loop than FGF9, helps keep the level of SOX9 high enough to activate other genes, such as Fgf9 and Sf1, which are necessary for the development of the male reproductive system. ^[8]
• PGD₂ plays a role in the attraction of neutrophils (chemotaxis).
• PGD₂-Adenosine system promotes sleep. ^{[9] [10] [11]}

Inhibitors

In silico simulations have predicted the following as potential inhibitors of PGD₂ synthase: ^[12]

• Acteoside
• Amentoflavone
• Ricinoleic acid
• Rutin
• Hinokiflavone
• Vitamin K and Vitamin D3 are natural inhibitors of Prostaglandin synthesis. ^{[13] [14] [15]}

See also

• PGD₂ synthase

References

1. Saito S, Tsuda H, Michimata T (May 2002). "Prostaglandin D2 and reproduction". American Journal of Reproductive Immunology. 47 (5): 295–302. doi:10.1034/j.1600-0897.2002.01113.x. PMID   12148545. S2CID   9284645.
2. Pettipher R, Hansel TT (2008). "Antagonists of the prostaglandin D2 receptor CRTH2" . Drug News & Perspectives. 21 (6): 317–22. doi:10.1358/dnp.2008.21.6.1246831. PMID   18836589 . Retrieved 9 April 2011.
3. Morrow, JD; Parsons Wg, 3rd; Roberts Lj, 2nd (August 1989). "Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid". Prostaglandins. 38 (2): 263–74. doi:10.1016/0090-6980(89)90088-9. PMID   2475889.
4. Garza, Luis A.; et al. (21 March 2012). "Prostaglandin D₂ Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia". Science Translational Medicine. 4 (126): 126ra34. doi:10.1126/scitranslmed.3003122. ISSN   1946-6234. PMC   3319975 . PMID   22440736.
5. Lee Phillips, Melissa (2012). "Clues to the cause of male pattern baldness". Nature. doi: 10.1038/nature.2012.10277 .
6. Onoe, H.; et al. (21 May 2012). "Prostaglandin D₂, a cerebral sleep-inducing substance in monkeys". Proceedings of the National Academy of Sciences of the United States of America. 85 (11): 4082–4086. doi: 10.1073/pnas.85.11.4082 . PMC   280366 . PMID   3163802.
7. Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM; et al. (2012). "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia". Sci Transl Med. 4 (126): 126ra34. doi:10.1126/scitranslmed.3003122. PMC   3319975 . PMID   22440736.
8. Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S; et al. (2009). "The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation". Development. 136 (11): 1813–21. doi:10.1242/dev.032631. PMC   4075598 . PMID   19429785.
9. Urade Y, Hayaishi O (2011). "Prostaglandin D2 and sleep/wake regulation". Sleep Med Rev. 15 (6): 411–8. doi:10.1016/j.smrv.2011.08.003. PMID   22024172.
10. Nagata N, Urade Y (2012). "[Sleep-wake regulation by prostaglandin D2 and adenosine]". Brain Nerve. 64 (6): 621–8. PMID   22647469.
11. Ahmad AS, Ottallah H, Maciel CB, Strickland M, Doré S (2019). "Role of the L-PGDS-PGD2-DP1 receptor axis in sleep regulation and neurologic outcomes". Sleep. 42 (6). doi:10.1093/sleep/zsz073. PMC   6559173 . PMID   30893431.
12. Fong, Pedro; Tong, Henry H. Y.; Ng, Kin H.; Lao, Cheng K.; Chong, Chon I.; Chao, Chi M. (4 December 2015). "In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss". Journal of Ethnopharmacology. 175: 470–480. doi:10.1016/j.jep.2015.10.005. ISSN   1872-7573. PMID   26456343.
13. Kieronska-Rudek A, Kij A, Kaczara P, Tworzydlo A, Napiorkowski M, Sidoryk K; et al. (2021). "Exogenous Vitamins K Exert Anti-Inflammatory Effects Dissociated from Their Role as Substrates for Synthesis of Endogenous MK-4 in Murine Macrophages Cell Line". Cells. 10 (7): 1571. doi: 10.3390/cells10071571 . PMC   8303864 . PMID   34206530.
14. Koshihara Y, Hoshi K, Shiraki M (1993). "Vitamin K2 (menatetrenone) inhibits prostaglandin synthesis in cultured human osteoblast-like periosteal cells by inhibiting prostaglandin H synthase activity". Biochem Pharmacol. 46 (8): 1355–62. doi:10.1016/0006-2952(93)90099-i. PMID   8240383.
15. Krishnan AV, Srinivas S, Feldman D (2009). "Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer". Dermatoendocrinol. 1 (1): 7–11. doi:10.4161/derm.1.1.7106. PMC   2715203 . PMID   20046582.