Prostaglandin D2
(Redirected fromPGD2)
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| IUPAC name
9α,15S-Dihydroxy-11-oxo-prosta-5Z,13E-dien-1-oic acid
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3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.164.741 |
| KEGG | |
| MeSH | Prostaglandin+D2 |
PubChemCID
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| UNII | |
CompTox Dashboard(EPA)
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| Properties | |
| C20H32O5 | |
| Molar mass | 352.471g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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Prostaglandin D2(orPGD2) is aprostaglandinthat binds to the receptorPTGDR(DP1), as well asCRTH2(DP2).[1][2]It is a major prostaglandin produced bymast cells– recruitsTh2 cells,eosinophils,andbasophils.In mammalian organs, large amounts of PGD2are found only in thebrainand in mast cells. It is critical to development ofallergicdiseases such asasthma. Research carried out in 1989[3]found PGD2is the primary mediator of vasodilation (the "niacin flush" ) after ingestion ofniacin(nicotinic acid).
A 2012 research paper indicates a causal link between elevated levels of localized PGD2and hair growth inhibition.[4]Applied topically, the researchers found PGD2prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2had inhibited hair growth. The researchers also found PGD2levels were much higher in balding scalp tissue than nonbalding scalp tissue, through increased levels ofprostaglandin D2 synthase.The paper suggested that inhibition of hair growth involved binding of PGD2to a receptor called GPR44, and that GPR44 therefore would be atherapeutic targetforandrogenic alopeciain 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 PGD2through blocking the GPR44 are already in clinical trials.[5]
Production
[edit]- Cellular synthesis occurs through thearachidonic acidcascade with the final conversion fromPGH2done byPGD2synthase(PTGDS).
- In the brain, production occurs via an alternative pathway through the soluble, secretedenzymeβ-trace[6]
Effects
[edit]- PGD2promotesbronchoconstrictionandvasoconstrictionduring times ofInflammationto 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 withallergens,air pollution,secondhand smokeandsmoke.
- PGD2 is involved in the regulation of reducing body temperature in sleep, and acts opposite toPGE2.
- Elevated levels of PGD2andPGD2synthasein scalp hair follicles may be partially responsible formale pattern baldness.[7]
- PGD2also plays a part in male sexual development. It forms a feedforward loop withSox9,which is activated by theSRYof theY chromosome.PGD2, in a different feedforward loop thanFGF9,helps keep the level ofSOX9high enough to activate other genes, such as Fgf9 andSf1,which are necessary for the development of the male reproductive system.[8]
- PGD2plays a role in the attraction ofneutrophils(chemotaxis).
- PGD2-Adenosinesystem promotes sleep.[9][10][11]
Inhibitors
[edit]In silicosimulations have predicted the following as potentialinhibitorsof PGD2synthase:[12]
- Acteoside
- Amentoflavone
- Ricinoleic acid
- Rutin
- Hinokiflavone
- Vitamin KandVitamin D3are natural inhibitors of Prostaglandin synthesis.[13][14][15]
See also
[edit]References
[edit]- ^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.PMID12148545.S2CID9284645.
- ^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.PMID18836589.Retrieved9 April2011.
- ^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.PMID2475889.
{{cite journal}}:CS1 maint: numeric names: authors list (link) - ^Garza, Luis A.; et al. (21 March 2012)."Prostaglandin D2Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia ".Science Translational Medicine.4(126): 126ra34.doi:10.1126/scitranslmed.3003122.ISSN1946-6234.PMC3319975.PMID22440736.
- ^abLee Phillips, Melissa (2012)."Clues to the cause of male pattern baldness".Nature.doi:10.1038/nature.2012.10277.
- ^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.PMC280366.PMID3163802.
- ^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.PMC3319975.PMID22440736.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^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.PMC4075598.PMID19429785.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^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.PMID22024172.
- ^Nagata N, Urade Y (2012)."[Sleep-wake regulation by prostaglandin D2 and adenosine]".Brain Nerve.64(6): 621–8.PMID22647469.
- ^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.PMC6559173.PMID30893431.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^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.ISSN1872-7573.PMID26456343.
- ^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.PMC8303864.PMID34206530.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^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.PMID8240383.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^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.PMC2715203.PMID20046582.
{{cite journal}}:CS1 maint: multiple names: authors list (link)