Prostaglandin D₂ (or PGD₂) is a

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

that binds to the receptor PTGDR (DP₁), as well as

CRTH2 Prostaglandin D2 receptor 2 (DP2 or CRTH2) is a human protein encoded by the PTGDR2 gene and GPR44. DP2 has also been designated as CD294 (cluster of differentiation 294). It is a member of the class of prostaglandin receptors which bind with and ...

(DP₂). It is a major prostaglandin produced by

mast cells A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

– recruits

Th2 cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

, and

basophils Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...

. In mammalian organs, large amounts of PGD₂ are found only in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

and in mast cells. It is critical to development of

allergic Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic der ...

diseases such as

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

. Research carried out in 1989' found PGD₂ is the primary mediator of vasodilation (the "niacin flush") after ingestion of

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

(nicotinic acid). 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 Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the ''PTGDS'' gene. Function The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin ...

. 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 Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

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.

Production

*Cellular synthesis occurs through the

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...

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 Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

β-trace

Effects

*PGD₂ causes a contraction of the

bronchial A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...

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 . *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 Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

. *PGD₂ also plays a part in male sexual development. It forms a feedforward loop with

Sox9 Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene. Function SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...

, which is activated by the SRY of the

Y chromosome The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...

. PGD2, in a different feedforward loop than

FGF9 Glia-activating factor is a protein that in humans is encoded by the ''FGF9'' gene. Function The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival ...

, helps keep the level of

SOX9 Transcription factor SOX-9 is a protein that in humans is encoded by the ''SOX9'' gene. Function SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but no ...

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 Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

(

chemotaxis Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...

). *PGD₂ with

Adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...

promotes sleep.

Inhibitors

In silico In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...

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

Ricinoleic acid Ricinoleic acid, formally called 12-hydroxy-9-''cis''-octadecenoic acid is a fatty acid. It is an unsaturated omega-9 fatty acid and a hydroxy acid. It is a major component of the seed oil obtained from mature castor plant (''Ricinus communis' ...

* Acteoside *

Amentoflavone Amentoflavone is a biflavonoid (''bis''-apigenin coupled at 8 and 3' positions, or 3′,8′′-biapigenin) constituent of a number of plants including ''Ginkgo biloba'', ''Chamaecyparis obtusa'' (hinoki), '' Hypericum perforatum'' (St ...

Rutin Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside combining the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose). It is a flavonoid found in a wide variety of pla ...

* Hinokiflavone Natural inhibitors of Prostaglandin synthesis including PGD₂ are

Vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...

and

Vitamin D3 Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement. Cholecalciferol is made in the skin f ...

References

{{Prostanoidergics Prostaglandins

Production

Effects

Inhibitors

See also

References