Prostaglandin E 2
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| Surname | Prostaglandin E2 | |||||||||||||||||||||
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| Molecular formula | C 20 H 32 O 5 | |||||||||||||||||||||
| Brief description |
white solid |
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| Molar mass | 352.47 g mol −1 | |||||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
65-70 ° C |
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| solubility |
poor in acetone (10 g l −1 at 20 ° C) |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||||||||
Prostaglandin E 2 belongs to the group of prostaglandins . It is synthesized from prostaglandin H 2 by prostaglandin E synthase .
Effects
Prostaglandin E 2 binds to four sub-forms of G-protein-coupled membrane receptors EP1 - EP4 and develops different effects through it.
inflammation
PGE 2 , together with PGI 2, is the main prostaglandin involved in the inflammatory process. It increases vascular permeability (tissue swelling), is involved in the development of reddening and intensifies pain (which is caused by other inflammatory substances such as bradykinin or histamine ) by sensitizing nociceptive nerve endings (by setting the activation threshold for tetrodotoxin-resistant sodium channels on sensory nerves lowers).
fever
Fever is partly caused by PGE 2 , which is released by endothelial cells in the vessels of the hypothalamus . Bacterial lipopolysaccharides and interleukin-1β stimulate cyclooxygenase-2 and prostaglandin E synthase in the endothelial cells that form the blood-brain barrier . The PGE 2 diffuses into the region of the organum vasculosum laminae terminalis (OLVT) of the hypothalamus, from where the fever reaction is controlled. There, the EP3 receptor is activated by the PGE 2 .
immune system
Immune system cells such as macrophages and monocytes that are stimulated by inflammatory mediators secrete large amounts of PGE 2 along with TXA 2 . Neutrophils produce moderate amounts of PGE 2 . Lymphocytes and mast cells (these form prostaglandin D2 ) do not form PGE 2 .
Since PGE 2 leads to an increase in cAMP , the secretion of PGE 2 by macrophages can serve as negative feedback in order to limit the inflammatory activity. PGE 2 inhibits interleukin-2 and interferon-γ production by T lymphocytes as well as interleukin-1β and TNFα release from macrophages. PGE 2, on the other hand, increases interleukin-6 synthesis.
Immature thymocytes are stimulated to mature and differentiate by PGE 2 .
Different tumor cells produce large amounts of PGE 2 . It is believed that this is why the immune system can be inhibited in cancer.
stomach
PGE 2 is formed by the mucous membrane cells and cells of the smooth muscles of the stomach and protects it, which is mainly caused by a combination of three mechanisms:
- PGE 2 (via the EP3 receptors ) reduces (together with PGI 2 via the prostacyclin receptor ) the secretion of gastric acid by the parietal cells of the stomach.
- PGE 2 (like PGI 2 ) increases the blood flow to the gastric mucosa.
- PGE 2 (which is produced by the gastric mucosal cells or given into the stomach) stimulates (also via the EP3 receptors ) the release of viscous mucus and neutralizing bicarbonate , which protects the gastric mucosa from its own acid.
The risk of developing gastric ulcers increases when both cyclooxygenases ( COX-1 and COX-2 ) are inhibited with drugs and the formation of prostaglandin in the stomach is severely restricted.
PGE 2 also stimulates the EP1 receptors in the gastric smooth muscle cells, causing them to contract.
Cardiovascular system
- In contrast to prostacyclin , PGE 2 can cause either vasoconstriction or vasodilation: it depends on the vessel and the type of prostaglandin E receptors that are expressed in their smooth muscle cells.
- PGE 2 stimulates the formation of new vessels by inducing the vascular endothelial growth factor . To what extent and with what relevance this happens is still unclear (status 2004).
- Keeps the ductus arteriosus (via the EP4 receptor ) open.
Kidneys
PGE 2 is the main prostaglandin (in addition to smaller amounts of prostacyclin and very small amounts of TXA 2 ), which is formed in the kidney cortex . However, the renal medulla still produces up to 20 times more PGE 2 than the renal cortex. The PGE 2 formation in the kidneys can be estimated from the urine excretion of PGE 2 .
- PGE 2 and prostacyclin have a vasodilator and blood flow increasing function in the kidneys. The blood flow to the kidneys is dependent on PGE 2 and prostacyclin in various basic diseases ( heart failure , liver cirrhosis , renal failure ) . Therefore, if prostaglandin synthesis is inhibited by NSAIDs, these patients are at risk of serious renal impairment . Cyclooxygenase-1 is particularly important here, only some cells of the macula densa contain cyclooxygenase-2 .
- They inhibit the reabsorption of sodium in the renal tubule system .
- In the epithelial cells of the glomerulum and in the mesangium, PGE 2 and prostacyclin are also formed (mainly by cyclooxygenase-2 ) ; there they stimulate renin secretion .
Lungs
PGE 2 (like prostacyclin ) is a weak bronchodilator (while thromboxane , PGD 2 and PGF 2α are strong bronchoconstrictors ). Inflammation mediators in the lungs mainly stimulate cyclooxygenase-2 , the stimulation of which mainly leads to an increased formation of PGE 2 (together with smaller amounts of prostacyclin, thromboxane and PGF 2α ). This prostaglandin formation is suppressed by dexamethasone . However, the role of prostaglandins in asthma for practical medicine remains unclear so far, since COX-2 inhibitors can not achieve any significant effect in practice. Acetylsalicylic acid often worsens asthma (through an increased formation of leukotrienes with an inhibition of cyclooxygenases ).
Central nervous system
In spinal PGE operates two pain-reinforcing . In the hypothalamus , it causes an increase in body temperature (including fever ) and alertness (and is therefore an antagonist to PGD 2 ).
Other effects
PGE 2 increases bone resorption and inhibits lipolysis .
Inhibition of biosynthesis
The flavonoid taxifolin inhibits u. a. the lipopolysaccharide- induced formation of prostaglandin E.
Trade names
Minprostin E2 (D), Prepidil (D, A), Propess (D, A, CH), Prostin (A, CH)
Individual evidence
- ↑ a b c d data sheet Prostaglandin E 2 from Sigma-Aldrich , accessed on October 18, 2016 ( PDF ).
- ↑ Data sheet Prostaglandin E 2 (PDF) from Calbiochem, accessed on December 8, 2015.
- ↑ a b c d e D. Simmons et al: Cyclooxygenase Isoenzymes: The Biology of Prostaglandin Synthesis and Inhibition. In: Pharmacol Rev. 2004; 56, pp. 387-437.
- ↑ SM Plaza, DW Lamson: Vitamin K2 in bone metabolism and osteoporosis. In: Alternative medicine review: a journal of clinical therapeutic. Volume 10, Number 1, March 2005, pp. 24-35, PMID 15771560 (review).
- ^ Y. Woo, SY hin, J. Hyun et al: Flavanones inhibit the clonogenicity of HCT116 cololectal cancer cells. In: International journal of molecular medicine. 2012 Mar; 29 (3), pp. 403-408, PMID 22160193 .
