Prostaglandin E2

• 7 - [3 -hydroxy-2 -(3- hydroxyoct -1-enyl ) - 5 -oxo- cyclopentyl] hept-5- enoic acid (IUPAC)
• Dinoprostone

G02AD02

White solid

65-70 ° C.

Poorly in acetone (10 g · l-1 at 20 ° C)

Risk

Template: Infobox chemical / molecular formula search available

Prostaglandin E2 is one of the group of prostaglandins. It is synthesized by the prostaglandin E synthase from prostaglandin H2.

• 2.1 inhibitors

Effects

Prostaglandin E2 binds to four subtypes of G protein-coupled membrane receptors EP1 - EP4 and deployed about different effects.

Inflammation

PGE2, together with the Hauptprostaglandin PGI2, which is involved in the inflammatory process. It increases vascular permeability ( tissue swelling), is involved in the development of redness and increases the pain (which is caused by other inflammatory substances such as bradykinin or histamine ) by sensitized nociceptive nerve endings ( by the activation threshold for tetrodotoxin-resistant sodium channels in sensory nerves decreases ).

Fever

Fever is contributed to by PGE2, which is released from endothelial cells of the vessels of the hypothalamus. Bacterial lipopolysaccharide and interleukin- 1β stimulate the cyclooxygenase -2 and prostaglandin E synthase in endothelial cells that form the blood -brain barrier. The PGE2 is diffused into the region of the Organum vasculosum laminae terminalis ( OLVT ) of the hypothalamus, where the reaction temperature is controlled. There the EP3 receptor is activated by PGE2.

Immune system

Cells of the immune system like macrophages and monocytes are stimulated by inflammatory mediators, secrete large amounts of PGE2 with TXA2. Neutrophils constitute moderate amounts of PGE2. Lymphocytes and mast cells ( prostaglandin D2 this form ) do not form a PGE2.

Since PGE2 leads to a cAMP increasing the secretion of PGE2 by macrophages may serve as a negative feedback to limit the inflammation activity. PGE2 inhibits the formation of interleukin-2 and interferon- γ production by T lymphocytes as well as the interleukin- 1β release, and TNF release from macrophages. However PGE2 enhances IL- 6 synthesis.

Immature thymocytes are stimulated by PGE2 for maturation and differentiation.

Various tumor cells produce large quantities of PGE2. It is thought that, therefore, can be inhibited in cancer, the immune system.

Stomach

PGE2 is formed by the mucosal cells and smooth muscle cells of the stomach and protects it, which is caused primarily by a combination of three mechanisms:

The risk to form ulcers, when both cyclooxygenase (COX -1 and COX -2) are inhibited, and so the drug prostaglandins in the stomach is greatly limited increases.

PGE2 also stimulates the EP1 receptors of the smooth muscle of the stomach and leads to the contraction.

Cardiovascular System

• In contrast to prostacyclin, PGE 2 can trigger either a vasoconstriction or vasodilatation: depending on the vessel and the nature of the prostaglandin E receptor which are expressed in their smooth muscle cells.
• PGE2 stimulates angiogenesis by inducing the vascular endothelial growth factor. In what context and with what relevance this happens is still unclear (as of 2004).
• Keeps the ductus arteriosus open (via the EP4 receptor).

Kidneys

PGE2 is the Hauptprostaglandin (in addition to smaller amounts of prostacyclin and very small amounts of TXA2 ), which is formed in the renal cortex. However, the renal medulla produces even up to 20 times more PGE2 than the renal cortex. On the urinary excretion of PGE2 can be estimated PGE2 formation in the kidney.

• PGE2 and prostacyclin have a vasodilator and circulation- enhancing function in the kidney. The renal blood flow varies with different underlying diseases (heart failure, liver cirrhosis, renal failure) depends on PGE2 and prostacyclin. Therefore, in these patients the risk of serious renal perfusion disturbance when the prostaglandin synthesis by NSAIDs is inhibited. This is especially the cyclooxygenase-1 significantly, only a few cells of the macula densa include cyclooxygenase -2.
• They inhibit the Rückresorbtion of sodium in the Nierentubulussystem.
• In the epithelial cells of the glomerulus and in the mesangium also be formed (especially by cyclooxygenase -2) PGE2 and prostacyclin; there they stimulate renin secretion.

Lungs

PGE2 (such as prostacyclin ) a weak bronchodilator ( while thromboxane, PGD2 and PGF2 are strong bronchoconstrictors ). Entzündungsmediatioren in the lungs stimulate especially cyclooxygenase - 2, the stimulation leads mainly to the formation of a multi- PGE2 (along with minor amounts of prostacyclin, thromboxane, and PGF2 ). This prostaglandin is suppressed by dexamethasone. However, the role of prostaglandins in asthma for practical medicine remains unclear, since in practice no significant effect can be achieved by COX - 2 inhibitors. Acetylsalicylic acid worsens asthma often (due to an increased formation of leukotrienes in an inhibition of cyclooxygenase ).

Central Nervous System

In the spinal cord PGE2 has a pain- reinforcing. In the hypothalamus, it causes an increase in body temperature (including fever) and alertness ( and thus is there an opponent to PGD2 ).

Bone

PGE2 increases bone resorption.

Further effects

• Inhibits lipolysis

Regulation

Inhibitors

The flavonoid taxifolin inhibits inter alia, the production of lipopolysaccharide -induced prostaglandin E.

Trade names

Minprostin E2 ( D), Prepidil (D, A), PROPESS (D, A, CH), PROSTIN (A, CH)