Prostaglandin D2: Difference between revisions

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

| Verifiedfields = changed

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| verifiedrevid = 438483782

| ImageFile = Prostaglandin D2.svg

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

| OtherNames =

|Section1={{Chembox Identifiers

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

| CASNo = 41598-07-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = RXY07S6CZ2

| PubChem = 448457

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 15555

| IUPHAR_ligand2 = 1891

| MeSHName = Prostaglandin+D2

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| 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

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = BHMBVRSPMRCCGG-OUTUXVNYSA-N

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| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = C00696

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|Section2={{Chembox Properties

| C = 20 | H = 32 | O = 5

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|Section3={{Chembox Hazards

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'''Prostaglandin D₂''' (or '''PGD₂''') is a [[prostaglandin]] that binds to the receptor [[PTGDR]] (DP₁), as well as [[CRTH2]] (DP₂).<ref name="pmid12148545">{{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 }}</ref><ref name="pmid18836589">{{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}}</ref> 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 [[allergy|allergic]] diseases such as [[asthma]].

Research carried out in 1989''<ref>{{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}}</ref>'' found PGD₂ is the primary mediator of vasodilation (the "niacin flush") after ingestion of [[Niacin (substance)|niacin]] (nicotinic acid).

A 2012 research paper <!--published in the journal [[Science Translational Medicine]]--> indicates a causal link between elevated levels of localized PGD₂ and hair growth inhibition.<ref name=Garza_et_al_2012>{{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}}</ref> 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 receptor called GPR44, and that GPR44 therefore would be a [[Biological target|therapeutic target]] for [[androgenic alopecia]] in both men and women with hair loss and thinning.<ref name="garza_nature_article">{{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}}</ref> 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 GPR44 are already in clinical trials.<ref name="garza_nature_article" />

==Production==

*Cellular synthesis occurs through the [[arachidonic acid]] cascade with the final conversion from [[prostaglandin H2|PGH₂]] done by [[Prostaglandin D2 synthase|PGD₂ synthase]] (PTGDS).

*In the brain, production occurs via an alternative pathway through the soluble, secreted [[enzyme]] β-trace <ref name=Onoe_et_al_1988>{{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}}</ref>

*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 [[prostaglandin E2|PGE₂]].

*Elevated levels of PGD₂ and [[Prostaglandin D2 synthase|PGD₂ synthase]] in scalp hair follicles may be partially responsible for [[androgenic alopecia|male pattern baldness]].<ref name="pmid22440736">{{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 }} </ref>

*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 (gene)|Sf1]], which are necessary for the development of the male reproductive system.<ref name="pmid19429785">{{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 }} </ref>

*PGD₂ plays a role in the attraction of [[neutrophils]] ([[chemotaxis]]).

*PGD₂-[[Adenosine]] system promotes sleep.<ref name="pmid22024172">{{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 }} </ref><ref name="pmid22647469">{{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 }} </ref><ref name="pmid30893431">{{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 }} </ref>

== Inhibitors ==

[[In silico]] simulations have predicted the following as potential [[Enzyme inhibitor|inhibitors]] of PGD₂ synthase:<ref>{{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}}</ref>

* [[Verbascoside|Acteoside]]

* [[Amentoflavone]]

* [[Ricinoleic acid]]

* [[Rutin]]

* Hinokiflavone

* [[Vitamin K]] and [[Vitamin D3]] are natural inhibitors of Prostaglandin synthesis.<ref name="pmid34206530">{{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}} </ref><ref name="pmid8240383">{{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 }} </ref><ref name="pmid20046582">{{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 }} </ref>

* [[Prostaglandin D2 synthase|PGD₂ synthase]]

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{{Prostanoidergics}}