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Prostaglandin D2

{{DISPLAYTITLE:Prostaglandin D2}}

{{Use dmy dates|date=October 2019}}

{{Chembox

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| ImageFile = Prostaglandin D2.svg

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| IUPACName = 9α,15S-Dihydroxy-11-oxo-prosta-5Z,13E-dien-1-oic acid

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|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|??}}

| CASNo = 41598-07-6

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| PubChem = 448457

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| ChEBI = 15555

| IUPHAR_ligand = 1881

| IUPHAR_ligand2 = 1891

| MeSHName = Prostaglandin+D2

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| ChemSpiderID = 395250

| SMILES = CCCCC[C@@H](/C=C/[C@@H]1[C@H]([C@H](CC1=O)O)C/C=C\CCCC(=O)O)O

| 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

| InChIKey = BHMBVRSPMRCCGG-OUTUXVNYBP

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| StdInChI = 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

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| StdInChIKey = BHMBVRSPMRCCGG-OUTUXVNYSA-N

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| KEGG = C00696

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Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2).{{cite journal |vauthors=Saito S, Tsuda H, Michimata T | title = Prostaglandin D2 and reproduction | journal = American Journal of Reproductive Immunology | volume = 47 | issue = 5 | pages = 295–302 |date=May 2002 | pmid = 12148545 | doi = 10.1034/j.1600-0897.2002.01113.x| s2cid = 9284645 }}{{cite journal |vauthors=Pettipher R, Hansel TT | title = Antagonists of the prostaglandin D2 receptor CRTH2 | journal = Drug News & Perspectives | volume = 21 | issue = 6 | pages = 317–22 | year = 2008 | pmid = 18836589 | doi = 10.1358/dnp.2008.21.6.1246831 | url = http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=3&p_RefId=1246831| access-date = 2011-04-09| url-access = subscription }} 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{{cite journal |pmid = 2475889 | volume=38 | issue=2 | title=Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid |date=August 1989 | journal=Prostaglandins | pages=263–74 |last1 = Morrow |first1 = JD |last2 = Parsons Wg |first2 = 3rd |last3 = Roberts Lj |first3 = 2nd | doi=10.1016/0090-6980(89)90088-9}} 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.{{Cite journal| doi = 10.1126/scitranslmed.3003122| issn = 1946-6234| volume = 4| issue = 126| pages = 126ra34| last1 = Garza| first1 = Luis A.| title = Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia| journal = Science Translational Medicine| date = 2012-03-21| pmid=22440736| pmc=3319975| last2 = Liu| first2 = Y.| last3 = Yang| first3 = Z.| last4 = Alagesan| first4 = B.| last5 = Lawson| first5 = J. A.| last6 = Norberg| first6 = S. M.| last7 = Loy| first7 = D. E.| last8 = Zhao| first8 = T.| last9 = Blatt| first9 = H. B.| display-authors = 1}} 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.{{cite journal|url=http://www.nature.com/news/clues-to-the-cause-of-male-pattern-baldness-1.10277|title=Clues to the cause of male pattern baldness|journal=Nature|doi=10.1038/nature.2012.10277|year=2012|last1=Lee Phillips|first1=Melissa|doi-access=free}} 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.

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 {{Cite journal| doi = 10.1073/pnas.85.11.4082|volume = 85| issue = 11| pages = 4082–4086| last1 = Onoe| first1 = H.| title = Prostaglandin D2, a cerebral sleep-inducing substance in monkeys| journal = Proceedings of the National Academy of Sciences of the United States of America| date = 2012-05-21| pmid=3163802| pmc=280366| last2 = Ueno| first2 = R| last3 = Fujita| first3 = I| last4 = Nishino| first4 = H| last5 = Oomura| first5 = Y| last6 = Hayaishi| first6 = O|display-authors = 1|doi-access = free}}

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.{{cite journal| author=Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM | display-authors=etal| title=Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. | journal=Sci Transl Med | year= 2012 | volume= 4 | issue= 126 | pages= 126ra34 | pmid=22440736 | doi=10.1126/scitranslmed.3003122 | pmc=3319975 }}
  • 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.{{cite journal| author=Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S | display-authors=etal| title=The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. | journal=Development | year= 2009 | volume= 136 | issue= 11 | pages= 1813–21 | pmid=19429785 | doi=10.1242/dev.032631 | pmc=4075598 }}
  • PGD2 plays a role in the attraction of neutrophils (chemotaxis).
  • PGD2-Adenosine system promotes sleep.{{cite journal| author=Urade Y, Hayaishi O| title=Prostaglandin D2 and sleep/wake regulation. | journal=Sleep Med Rev | year= 2011 | volume= 15 | issue= 6 | pages= 411–8 | pmid=22024172 | doi=10.1016/j.smrv.2011.08.003 | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/22024172 }} {{cite journal| author=Nagata N, Urade Y| title=[Sleep-wake regulation by prostaglandin D2 and adenosine]. | journal=Brain Nerve | year= 2012 | volume= 64 | issue= 6 | pages= 621–8 | pmid=22647469 | doi= | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/22647469 }} {{cite journal| author=Ahmad AS, Ottallah H, Maciel CB, Strickland M, Doré S| title=Role of the L-PGDS-PGD2-DP1 receptor axis in sleep regulation and neurologic outcomes. | journal=Sleep | year= 2019 | volume= 42 | issue= 6 | pages= | pmid=30893431 | doi=10.1093/sleep/zsz073 | pmc=6559173 }}

Inhibitors

In silico simulations have predicted the following as potential inhibitors of PGD2 synthase:{{Cite journal|last1=Fong|first1=Pedro|last2=Tong|first2=Henry H. Y.|last3=Ng|first3=Kin H.|last4=Lao|first4=Cheng K.|last5=Chong|first5=Chon I.|last6=Chao|first6=Chi M.|date=2015-12-04|title=In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss|journal=Journal of Ethnopharmacology|volume=175|pages=470–480|doi=10.1016/j.jep.2015.10.005|issn=1872-7573|pmid=26456343}}

  • Acteoside
  • Amentoflavone
  • Ricinoleic acid
  • Rutin
  • Hinokiflavone
  • Vitamin K and Vitamin D3 are natural inhibitors of Prostaglandin synthesis.{{cite journal| author=Kieronska-Rudek A, Kij A, Kaczara P, Tworzydlo A, Napiorkowski M, Sidoryk K | display-authors=etal| title=Exogenous Vitamins K Exert Anti-Inflammatory Effects Dissociated from Their Role as Substrates for Synthesis of Endogenous MK-4 in Murine Macrophages Cell Line. | journal=Cells | year= 2021 | volume= 10 | issue= 7 | page=1571| pmid=34206530 | doi=10.3390/cells10071571 | pmc=8303864 | doi-access=free}} {{cite journal| author=Koshihara Y, Hoshi K, Shiraki M| title=Vitamin K2 (menatetrenone) inhibits prostaglandin synthesis in cultured human osteoblast-like periosteal cells by inhibiting prostaglandin H synthase activity. | journal=Biochem Pharmacol | year= 1993 | volume= 46 | issue= 8 | pages= 1355–62 | pmid=8240383 | doi=10.1016/0006-2952(93)90099-i | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/8240383 }} {{cite journal| author=Krishnan AV, Srinivas S, Feldman D| title=Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer. | journal=Dermatoendocrinol | year= 2009 | volume= 1 | issue= 1 | pages= 7–11 | pmid=20046582 | doi=10.4161/derm.1.1.7106 | pmc=2715203 }}

See also

References

{{Reflist}}

{{Prostaglandins}}

{{Prostanoidergics}}

Category:Prostaglandins