Prostaglandin

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Prostaglandins
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E1 - Alprostadil
I2 - Prostacyclin

Prostaglandins (PG) are a group of

5-carbon ring. They are a subclass of eicosanoids and of the prostanoid
class of fatty acid derivatives.

The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues in some cases. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of

paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. Prostaglandins differ from endocrine hormones
in that they are not produced at a specific site but in many places throughout the human body.

Prostaglandins are powerful, locally-acting

vasoconstrictors and facilitate platelet aggregation. Their name comes from their role in clot formation (thrombosis
).

Specific prostaglandins are named with a letter indicating the type of ring structure, followed by a number indicating the number of double bonds in the hydrocarbon structure. For example, prostaglandin E1 has the abbreviation PGE1 and prostaglandin I2 has the abbreviation PGI2.

History and name

Systematic studies of prostaglandins began in 1930, when Kurzrock and Lieb found that human seminal fluid caused either stimulation or relaxation of strips of isolated human uterus. They noted the curious finding that uteri from patients who had gone through successful pregnancies responded to the fluid with relaxation, while uteri from sterile women responded with contraction upon addition of this seminal fluid.

E. J. Corey in 1969,[9] an achievement for which he was awarded the Japan Prize
in 1989.

In 1971, it was determined that

John R. Vane jointly received the 1982 Nobel Prize in Physiology or Medicine for their research on prostaglandins.[citation needed
]

Biochemistry

Biosynthesis

Biosynthesis of eicosanoids

Prostaglandins are found in most tissues and organs. They are

paracrine lipid mediators that act upon platelets, endothelium, uterine and mast cells. They are synthesized in the cell from the fatty acid arachidonic acid.[2]

leukotrienes.[citation needed
]

Release of prostaglandins from the cell

Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. The discovery of the

ATP-binding cassette transporter superfamily. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear.[citation needed
]

Cyclooxygenases

Prostaglandins are produced following the sequential oxygenation of arachidonic acid, DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases. The classic dogma is as follows:

  • COX-1
    is responsible for the baseline levels of prostaglandins.
  • COX-2
    produces prostaglandins through stimulation.

However, while COX-1 and COX-2 are both located in the

growth
.

Prostaglandin E synthase

Prostaglandin E2 (PGE2) — the most abundant prostaglandin[10] — is generated from the action of prostaglandin E synthases on prostaglandin H2 (prostaglandin H2, PGH2). Several prostaglandin E synthases have been identified. To date, microsomal (named as misoprostol) prostaglandin E synthase-1 emerges as a key enzyme in the formation of PGE2.[citation needed]

Other terminal prostaglandin synthases

Terminal prostaglandin synthases have been identified that are responsible for the formation of other prostaglandins. For example, hematopoietic and

PGD2 from PGH2. Similarly, prostacyclin (PGI2) synthase (PGIS) converts PGH2 into PGI2. A thromboxane synthase (TxAS
) has also been identified.
Prostaglandin-F synthase (PGFS) catalyzes the formation of 9α,11β-PGF2α,β from PGD2 and PGF2α from PGH2 in the presence of NADPH. This enzyme has recently been crystallized in complex with PGD2[11] and bimatoprost[12]
(a synthetic analogue of PGF2α).

Functions

There are currently ten known

PGD2
).

The diversity of receptors means that prostaglandins act on an array of cells and have a wide variety of effects such as:

  • create eicosanoids hormones
  • acts on thermoregulatory center of hypothalamus to produce fever
  • increases mating behaviors in goldfish[13]
  • Prostaglandins are released during
    endometrial cells, and the resultant release of their contents.[14][needs update] Release of prostaglandins and other inflammatory mediators in the uterus cause the uterus to contract. These substances are thought to be a major factor in primary dysmenorrhea.[15][16][17]

Types

The following is a comparison of different types of prostaglandin, including prostaglandin I2 (prostacyclin; PGI2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and prostaglandin F2α (PGF2α).[18]

Type Receptor Receptor type Function
PGI2
 		IP
Gs
PGD2 PTGDR (DP1) and CRTH2 (DP2)
GPCR
  • produced by mast cells; recruits Th2 cells, eosinophils, and basophils
  • In mammalian organs, large amounts of PGD2 are found only in the brain and in mast cells
  • Critical to development of allergic diseases such as asthma
PGE2
EP1
Gq
EP2
Gs
EP3
Gi
Unspecified
PGF2α FP
Gq

Role in pharmacology

Inhibition

See also: Prostaglandin antagonist and Mechanism of action of aspirin

Examples of prostaglandin antagonists are:

Clinical uses

Synthetic prostaglandins are used:

Synthesis

The original synthesis of prostaglandins F2α and E2 is shown below. It involves a Diels–Alder reaction which establishes the relative stereochemistry of three contiguous stereocenters on the prostaglandin cyclopentane core.[31]

Diels-Alder in the total synthesis of prostaglandin F2α by E. J. Corey
Diels-Alder in the total synthesis of prostaglandin F2α by E. J. Corey

Prostaglandin stimulants

Cold exposure and IUDs may increase prostaglandin production.[32]

See also

References

  1. ^ "Eicosanoid Synthesis and Metabolism: Prostaglandins, Thromboxanes, Leukotrienes, Lipoxins". themedicalbiochemistrypage.org. Retrieved 2018-09-21.
  2. ^
    PMID 21508345
    .
  3. ISBN 0-87893-617-3
    .
  4. S2CID 85374636
    .
  5. S2CID 38622866
    .
  6. PMID 16994667
    .
  7. ISBN 978-0-230-30466-6
    .
  8. S2CID 220151673
    .
  9. ISBN 3-527-29284-5
    .
  10. PMID 27230680
    . Prostaglandin E2 (PGE2) is the most abundant prostanoid in the human body
  11. PMID 14979715
    .
  12. PMID 16475787
    .
  13. ^ "Hormonal and pheromonal control of spawning in goldfish (PDF Download Available)". ResearchGate. Retrieved 2017-02-04.
  14. PMID 23440779
    .
  15. ISBN 0-7817-4363-X[page needed
    ]
  16. PMID 17174824
    .
  17. PMID 31535715
    .
  18. S2CID 1513449
    .
  19. ^
    ISBN 0-443-07145-4
    .
  20. PMID 11238561
    .
  21. PMID 17242161
    .
  22. PMID 32714206
    .
  23. ISBN 978-0-323-05908-4
    .
  24. PMID 34206530.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  25. PMID 8240383.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  26. PMID 20046582.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  27. ^ "WHO Recommendations for Induction of Labour". NCBI Bookshelf. Retrieved 2020-07-15. Induction of labour is defined as the process of artificially stimulating the uterus to start labour (1). It is usually performed by administering oxytocin or prostaglandins to the pregnant woman or by manually rupturing the amniotic membranes.
  28. ^ Medscape Early Penile Rehabilitation Helps Reduce Later Intractable ED
  29. PMID 25487360
    .
  30. ^ LaBonde, MS, DVM, Jerry. "Avian Reproductive and Pediatric Disorders" (PDF). Michigan Veterinary Medical Association. Archived from the original (PDF) on 2008-02-27. Retrieved 2008-01-26.{{cite web}}: CS1 maint: multiple names: authors list (link)
  31. PMID 5808505
    .
  32. ISBN 978-0-7817-9026-0
    .

External links
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