Prostaglandin d2

Prostaglandins, PG, are almost ubiquitously present in the organism and are characterized by a broad pharmacological spectrum of action. Prostaglandins belong to the eicosanoids and act as so-called tissue hormones. They are not normally stored in the various organs and cells, but are synthesized and released in response to various stimuli.

Substrates for the biosynthesis of prostaglandins are polyunsaturated C20 fatty acids such as arachidonic acid. The C20 fatty acids and their derivatives are also known as eicosanoids (from the Greek "είκοσι" [eikosi] = twenty).

The substrates of eicosanoid biosynthesis, such as arachidonic acid, are present in the cells for the most part in esterified form in the membrane phospholipids. The concentrations of free arachidonic acid, on the other hand, are very low. Only free arachidonic acid can serve as a substrate for cyclooxygenase or lipoxygenases. Eicosanoid biosynthesis therefore depends primarily on the release of C20 fatty acids from the membrane phospholipids. This occurs, for example, through the activity of the membrane-bound phospholipases A2 or C. Eicosanoid biosynthesis is activated by chemical, physiological, pathophysiological and pharmacological stimuli. Prostaglandins have a broad physiological and pathophysiological spectrum of action. They exert their effect via prostaglandin receptors. Prostaglandin receptors belong to the group of G-protein-coupled membrane receptors.

Prostaglandin D2 is a prostaglandin that binds to the receptor PTGDR (DP1) as well as to the receptor CRTH2 (CRTH2 receptor = chemoattractant receptor homologous molecule expressed on Th2-cells). Prostaglandin D2 is produced in mast cells and in the brain and is released cytosolically. Cytosolic PGD2 recruits Th2 cells, eosinophil granulocytes and basophil granulocytes.

It plays a pathogenetic role in the development and establishment of allergic diseases such as bronchial asthma and atopic dermatitis. PGD2 is the dominant prostanoid produced by activated mast cells. Its pathogenetic role in allergic diseases is not yet fully understood.

The CRTH2 receptor is a new type of receptor (for prostaglandin D2) that is selectively expressed on Th2 cells but not on Th1 cells. This provides a further approach for investigating the effect of the PGD2/CRTH2 axis in allergic diseases. In animal experiments, selective blockade of the CRTH2 receptor leads to a reduction in atopic inflammation.

PGD2 causes a contraction of the smooth muscles of the bronchial system. Its concentration is around 10 times higher in asthma patients after exposure to allergens than in healthy control patients.

PGD2 has a dilatory effect on blood vessels.

There is evidence that elevated local levels of PGD2 can lead to inhibition of hair growth. This observation could play a role in alopecia androgenetica. The prostaglandin D2 synthase (PTGDS) responsible for the formation of PGD2 is preferentially formed in the Sertoli cells. The production of this enzyme is not regulated by testosterone, but by progesterone and metabolites of vitamin A and D3.

PGD2 is involved in the regulation of body temperature during the sleep phase by lowering it. Protaglandin acts antagonistically to PGE2.

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