Eicosanoids are derived from 20-carbon polyunsaturated fatty acids and play important roles in human physiology. They include prostaglandins, thromboxanes, and leukotrienes, which are produced via the cyclooxygenase, lipoxygenase, and epoxygenase pathways. Specific eicosanoids have roles in inflammation and pain, vascular function, bronchial contraction, gastrointestinal function, and uterine contraction. Prostaglandins and leukotrienes are involved in processes like platelet aggregation, vasodilation, smooth muscle contraction, and inflammation. They are also used therapeutically to induce labor or abortion and maintain ductus arteriosus patency in newborns.

1. Eicosanoids and its
role in Human
Physiology
Dr. Anupam Mittal
MBBS, MD
King George’s Medical University, Lucknow

2. What is Eicosanoids?
• Greek: eikosi / “eicosa” → twenty
• Derived from 20 C Poly - unsaturated Fatty Acids
• Produced by almost all mammalian cells
• Not synthesised in advance / stored : synthesised as and when needed

3. Primary Precursor of Eicosanoid
Arachidonic acid (w6)
A 20-carbon chain fatty acid that include cyclic ring structure

4. Major Classes :
• Prostnoids
1. Prostaglandins
2. Thromboxanes
• Prostacyclins
• Leukotrienes

5. Major Pathways
1. Cyclooxygenase Pathway
2. 5 – Lipoxygenase Pathway
3. Cytochrome P450 Epoxigenase Pathway

6. Moore, G.Y.; Pidgeon, G.P. Cross-Talk between Cancer Cells and the Tumour Microenvironment: The
Role of the 5-Lipoxygenase Pathway. Int. J. Mol. Sci. 2017, 18, 236.

7. Cyclooxygenase Pathway
PGD2 :
• Produced by Mast Cells
• Effect on inflammation in the asthmatic airways through
increased inflammatory cell chemotaxis and cytokine production

8. Domingo, C., Palomares, O., Sandham, D.A. et al. The prostaglandin D2 receptor 2 pathway in asthma: a
key player in airway inflammation. Respir Res 19, 189 (2018). https://doi.org/10.1186/s12931-018-0893-x

9. Cyclooxygenase Pathway
PGI2 / Prostacyclin :
• Produced primarily by endothelium of vessels
• Vasodilation
• Inhibits platelet aggregation

11. Cyclooxygenase Pathway
Thromboxane A2 :
• Produced primarily by platelet
• Promotes platelet aggregation
• Vasoconstriction

14. Ellinsworth, David & Shukla, Nilima & Fleming, Ingrid & Jeremy, Jamie. (2014). Interactions between
thromboxane A2, thromboxane/prostaglandin (TP) receptors, and endothelium-derived hyperpolarization.
Cardiovascular research. 102. 10.1093/cvr/cvu015.

15. Cyclooxygenase Pathway
PGE2 :
• Vasodilation
• Relaxes smooth muscle
• Use to induce labor

17. Cyclooxygenase Pathway
PGF2α :
• Vasoconstriction
• Contraction of smooth muscle
• Stimulates uterine contraction

18. 5 – Lipoxygenase Pathway
LTA4 :
• Produced in leukocytes, platelets, mast cells, and heart and lung
vascular tissues
• An unstable substance whose main function is to serve as a substrate
for the biosynthesis of other LTs.

19. 5 – Lipoxygenase Pathway
LTB4 :
• Increased chemotaxis of polymorphonuclear leukocytes
• Release of lysosomal enzymes
• Adhesion of white blood cells

20. 5 – Lipoxygenase Pathway
Peptido Leukotrienes : LTC4 —> LTD4 —> LTE4
• Contraction of smooth muscle • Bronchoconstriction
• Vasoconstriction • Increased vascular permeability
• Cysteinyl LTs makeup slow reacting substance of anaphylaxis
• Involved in the pathophysiology of Asthma

21. Tsai M-J, Chang W-A, Chuang C-H, Wu K-L, Cheng C-H, Sheu C-C, Hsu Y-L, Hung J-Y. Cysteinyl Leukotriene
Pathway and Cancer. International Journal of Molecular Sciences. 2022; 23(1):120.
https://doi.org/10.3390/ijms23010120

22. It’s role in Human Physiology

23. Inflammation & Pain
• PGE2 and PGI2  Increase in Blood flow
• PGE2  Pain
• HETEs and Leukotrienes B4  Chemotaxis
• LT D4 , LT E4  Bronchial Smooth Muscle contraction

24. Lihong Chen, Guangrui Yang, Tilo Grosser, Prostanoids and inflammatory pain, Prostaglandins & Other Lipid Mediators,
Volumes 104–105, 2013, Pages 58-66, ISSN 1098-8823, https://doi.org/10.1016/j.prostaglandins.2012.08.006.

25. Vascular Smooth Muscle
• PGE2 and PGI2 : Vasodilators in most vascular beds
• Thromboxane : Vasoconstrictor, Platelet aggregation

26. Blood
TXA2 : Stimulate Platelets aggregation
PGI2 : Inhibit Platelet aggregation
PGEs : Induce Erythropoiesis by stimulating release of
EPO
5-HPETE : Stimulate release of Histamine
PGI2 : Inhibit release of Histamine

27. Bronchial Smooth Muscle
• PGFs : Smooth muscle contraction
• PGEs : Smooth muscle relaxation
• Leukotrienes ( LD4 , LDE4 ) : Bronchoconstrictors

29. Tsai M-J, Chang W-A, Chuang C-H, Wu K-L, Cheng C-H, Sheu C-C, Hsu Y-L, Hung J-Y. Cysteinyl Leukotriene
Pathway and Cancer. International Journal of Molecular Sciences. 2022; 23(1):120.
https://doi.org/10.3390/ijms23010120

31. Gastrointestinal Tract
PGE2 and PGI2 : Inhibit Acid and Pepsinogen
(Stomach secretion)
Prostaglandins : Stimulates synthesis of protective mucus
in
( PGE2 and PGF2a ) both stomach and the intestine

32. Gastrointestinal Tract
PGE2 and PGF2a : Increase the rate of longitudinal contraction in the
gut
Leukotrienes : Potent stimulators of gastrointestinal smooth
muscle

33. Source: Goodman and Gilman's Manual of Pharmacology and Therapeutics, 2e

34. Uterine Smooth Muscle
(In Pregnant female)
• PGE2 and PGF2a : Uterine smooth muscle contraction
(In Non-Pregnant) – Variable response
• PGE2a : Uterine contraction
• PGE2 : Uterine relaxation

35. Therapeutic Abortion
Inducing abortion in the second trimester :
• Infusion of PGF2a (Carboprost tromethamine)
• Dinoprostone (PGE2)

36. Management of Ductus Arteriosus
Maintenance:
Produced by PGE1 infusion
• Maintain patency, which may be desirable before surgery