Prostaglandin

Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2).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 found PGD2 is the primary mediator of vasodilation (the "niacin flush") after ingestion of niacin (nicotinic acid).
プロスタグランジンD2（またはPGD2）は、受容体PTGDR（DP1）およびCRTH2（DP2）に結合するプロスタグランジンです。これは、マスト細胞によって産生される主要なプロスタグランジンであり、Th2細胞、好酸球、好塩基球を動員します。哺乳類の臓器では、大量のPGD2は脳と肥満細胞にのみ見られます。喘息などのアレルギー性疾患の発症には重要です。 1989年に実施された研究では、PGD2がナイアシン（ニコチン酸）の摂取後の血管拡張（「ナイアシンフラッシュ」）の主要なメディエーターであることがわかりました。

2012年の研究論文は、局所的なPGD2のレベルの上昇と発毛阻害との因果関係を示しています。局所的に適用すると、研究者らは、PGD2が発毛を防ぎ、遺伝的に高レベルのPGD2を産生する傾向があるマウスが発毛を阻害したことを発見しました。研究者らはまた、PGD2レベルが、プロスタグランジンD2シンターゼのレベルの増加を通じて、非脱毛頭皮組織よりも脱毛頭皮組織ではるかに高いことを発見しました。この論文は、発毛の阻害には、PGD2がGPR44と呼ばれる受容体に結合することを含み、したがって、GPR44は、脱毛と薄毛を伴う男性と女性の両方の男性型脱毛症の治療標的になることを示唆しました。 PGD​​2と喘息との関係は数年前から知られているため、GPR44を遮断することでPGD2の効果を低下させようとするいくつかの薬剤は、すでに臨床試験が行われています。
A 2012 research paper indicates a causal link between elevated levels of localized PGD2 and hair growth inhibition. 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. 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.
Contents

1 Production
2 Effects
3 Inhibitors
4 See also
5 References

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

Effects

PGD2 causes a contraction of the bronchial airways. Its concentration in asthma patients is 10 times higher than in control patients, especially after it is brought into contact with allergens.
It is involved in the regulation of reducing body temperature in sleep, and acts opposite to PGE2[citation needed].
It causes vasodilation at low doses
It causes vasoconstriction at high doses
Elevated levels of PGD2 and PGD2 synthase in scalp hair follicles may be partially responsible for male pattern baldness.
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
PGD2 plays a role in the attraction of neutrophils (chemotaxis).
PGD2 with Adenosine promotes sleep.

Inhibitors


In silico simulations have predicted the following as potential inhibitors of PGD2 synthase:

Ricinoleic acid
Acteoside
Amentoflavone
Rutin
Hinokiflavone

Natural inhibitors of Prostaglandin synthesis including PGD2 are Vitamin K and Vitamin D3