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 receptor called GPR44, and that GPR44 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 GPR44 are already in clinical trials.[5]
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]
^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.
^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.
^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.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^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. PMC3319975. PMID 22440736.
^ 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. PMID 3163802.
^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. PMID 22440736.{{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. PMID 19429785.{{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. PMID 22024172.
^Nagata N, Urade Y (2012). "[Sleep-wake regulation by prostaglandin D2 and adenosine]". Brain Nerve. 64 (6): 621–8. PMID 22647469.
^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. PMID 30893431.{{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. ISSN 1872-7573. PMID 26456343.
^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. PMID 34206530.{{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. PMID 8240383.{{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. PMID 20046582.{{cite journal}}: CS1 maint: multiple names: authors list (link)
December 15, 2023
prostaglandin, prostaglandin, pgd2, prostaglandin, that, binds, receptor, ptgdr, well, crth2, major, prostaglandin, produced, mast, cells, recruits, cells, eosinophils, basophils, mammalian, organs, large, amounts, pgd2, found, only, brain, mast, cells, critic. 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 Prostaglandin D2 NamesIUPAC name 9a 15S dihydroxy 11 oxo prosta 5Z 13E dien 1 oic acidIdentifiersCAS Number 41598 07 6 Y3D model JSmol Interactive imageChEBI CHEBI 15555 NChemSpider 395250 NECHA InfoCard 100 164 741IUPHAR BPS 18811891KEGG C00696 NMeSH Prostaglandin D2PubChem CID 448457UNII RXY07S6CZ2 YCompTox Dashboard EPA DTXSID30897162InChI 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 NKey BHMBVRSPMRCCGG OUTUXVNYSA N NInChI 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 s1Key BHMBVRSPMRCCGG OUTUXVNYBPSMILES CCCCC C H C C C H 1 C H C H CC1 O O C C C CCCC O O OPropertiesChemical formula C20H32O5Molar mass 352 465 g molExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references 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 receptor called GPR44 and that GPR44 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 GPR44 are already in clinical trials 5 Contents 1 Production 2 Effects 3 Inhibitors 4 See also 5 ReferencesProduction editCellular 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 b trace 6 Effects editPGD2 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 editIn 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 editPGD2 synthaseReferences 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 PMID 12148545 S2CID 9284645 Pettipher R Hansel TT 2008 Antagonists of the prostaglandin D2 receptor CRTH2 Drug News amp Perspectives 21 6 317 22 doi 10 1358 dnp 2008 21 6 1246831 PMID 18836589 Retrieved 9 April 2011 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 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint numeric names authors list link 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 a b Lee 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 PMC 280366 PMID 3163802 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 a href Template Cite journal html title Template Cite journal cite journal a 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 PMC 4075598 PMID 19429785 a href Template Cite journal html title Template Cite journal cite journal a 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 PMID 22024172 Nagata N Urade Y 2012 Sleep wake regulation by prostaglandin D2 and adenosine Brain Nerve 64 6 621 8 PMID 22647469 Ahmad AS Ottallah H Maciel CB Strickland M Dore 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 a href Template Cite journal html title Template Cite journal cite journal a 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 ISSN 1872 7573 PMID 26456343 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 a href Template Cite journal html title Template Cite journal cite journal a 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 PMID 8240383 a href Template Cite journal html title Template Cite journal cite journal a 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 PMC 2715203 PMID 20046582 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Retrieved from https en wikipedia org w index php title Prostaglandin D2 amp oldid 1172715729, wikipedia, wiki, book, books, library,
