Prostaglandins (Pg) are a group of physiologically active lipid substances that are formed in the body enzymatically from certain essential fatty acids and contain a 20-membered carbon chain. Prostaglandins are mediators with a pronounced physiological effect. They are derivatives of prostanoic acid . Prostaglandins, together with thromboxanes and prostacyclin, form a subclass of prostanoids, which in turn belong to the class of eicosanoids [1] . Prostaglandins are not mediators of pain. However, they increase the sensitivity of nociceptive receptors (sensitize them) to pain mediators, which are histamine and bradykinin . Non-steroidal anti-inflammatory drugs , blocking the cyclooxygenase (COX) enzyme, reduce the production of prostaglandins, inhibiting the development of the inflammatory process, or reducing pain.
Content
History
For the first time, prostaglandin was isolated in 1935 by the Swedish physiologist Ulf von Euler from seminal fluid , so the term βprostaglandinβ comes from the Latin name for the prostate gland ( lat. Glandula prostatica ) [2] . It later turned out that prostaglandins are synthesized in many tissues and organs. In 1971, John Wayne discovered that aspirin is an inhibitor of prostaglandin synthesis . For the study of prostaglandins, he and the Swedish biochemists Sune BergstrΓΆm and Bengt Samuelson received the 1982 Nobel Prize in Physiology or Medicine [3] .
Biochemistry
Biosynthesis
Prostaglandins are found in almost all tissues and organs. They are autocrine and paracrine lipid mediators that act on platelets , endothelium , uterus , mast cells and other cells and organs. Prostaglandins are synthesized from essential fatty acids (EFAs) [4] .
| Fatty acid | Type of NLC | Type of |
| Gamma linolenic acid (GLA) via DHA | Ο-6 | Type 1 |
| Arachidonic Acid (AA) | Ο-6 | Type 2 |
| Eicosapentaenoic Acid (EPA) | Ο-3 | Type 3 |
The intermediate product is formed under the action of phospholipase A2 , which is then converted either by cyclooxygenase or lipoxygenase pathway. The cyclooxygenase pathway synthesizes thromboxanes , prostacyclin and prostaglandins D, E and F. The lipoxygenase pathway, which is active in leukocytes and macrophages , forms leukotrienes .
Cell secretion
It was previously believed that after synthesis, prostaglandins leave the cell due to passive diffusion , since they have significant lipophilicity . However, a prostaglandin transporter protein (PGT, SLCO2A1) was later discovered that mediates cell uptake of prostaglandins. The secretion is carried out by other proteins: multidrug resistance protein 4 (MRP4, ABCC4) from the ATP-binding cassette transporter family and, possibly, other carriers that are still unknown.
Cyclooxygenase
The synthesis of prostaglandins is carried out in two stages: oxidation under the action of cyclooxygenase and final prostaglandin synthase. There are two types of cyclooxygenases: COX-1 and COX-2. It is believed that COX-1 determines the basal level of prostaglandins, and COX-2 triggers the synthesis of prostaglandins during stimulation (for example, with inflammation ).
Prostaglandin E-synthase
Prostaglandin E 2 (PGE 2 ) is formed by prostaglandin E synthase from prostaglandin H 2 (PHH 2 ). Several prostaglandin E synthases have been detected. It is believed that microsomal prostaglandin E-synthase-1 is a key form of an enzyme that synthesizes PGE 2 .
Functions
Comparison of different types of prostaglandins prostacyclin, prostaglandin E 2 (dinoprostone) and prostaglandin F 2Ξ± .
| Type of | Receptor | Function |
|---|---|---|
| Prostacyclin | IP |
|
| Prostaglandin E 2 | EP 1 |
|
| EP 2 |
| |
| EP 3 |
| |
| EPO |
| |
| Prostaglandin F 2Ξ± | FP |
|
See also
- Isoprostanes
Notes
- β The Eicosanoids // Peter Curtis-Prior (Editor) // ISBN 978-0-471-48984-9 654 pages // 2004 Wiley
- β Von Euler US. Γber die spezifische blutdrucksenkende Substanz des menschlichen Prostata- und Samenblasensekrets. Klin Wochenschr 1935; 14: 1182-1183.
- β The Nobel Prize in Physiology or Medicine 1982 Sune K. BergstrΓΆm, Bengt I. Samuelsson, John R. Vane
- β Dorlands Medical Dictionary [1] Archived September 14, 2007 at Wayback Machine URL reference on 10/23/05.
- β 1 2 Rang, HP Pharmacology. - 5th. - Edinburgh: Churchill Livingstone, 2003 .-- P. 234. - ISBN 0-443-07145-4 .
- β Fabre JE, Nguyen M, Athirakul K, Coggins K, McNeish JD, Austin S, Parise LK, FitzGerald GA, Coffman TM, Koller BH. Journal of Clinical investigation, 2001, 107: 603
- β Gross S, Tilly P, Hentsch D, Vonesch JL, Fabre JE. Journal of Experimental Medicine, 2007, 204: 311