Eicosanoids are cell-signaling molecules produced from arachidonic acid. With the action of phospholipase A2, arachidonic acid is released from the plasma membrane. The different families of eicosanoids, which are prostaglandins (PGs), thromboxanes (TXA2s), prostacyclin (PGI2), lipoxins (LXs), and leukotrienes (LTs), emerge from a series of reactions catalyzed by different enzymes. The LTs and LXs are products of the lipoxygenase (LOX) pathway. The remaining eicosanoids are produced from the COX pathway, which involves 2 enzymes, COX-1 and COX-2. Eicosanoids are involved in various physiological and pathological processes. Thromboxanes cause platelet aggregation and are potent vasoconstrictors. Leukotrienes mediate allergic responses, while LXs have anti-inflammatory activities. Principal actions of PGs include vasodilation, smooth muscle contraction, and inflammation. Prostacyclin, a member of the PG family, has a potent vasodilatory effect. Both biologic actions and inhibitions of eicosanoids are mechanisms used in pharmacologic agents for various medical conditions and desired clinical effects.

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  • Cell-signaling molecules
  • Produced from arachidonic acid (an abundant 20-carbon polyunsaturated fatty acid released from the plasma membrane through the activity of phospholipase A2)
  • Major families of eicosanoids: 
    • Prostanoids:
      • Thromboxanes (TXA2s)
      • Prostaglandins (PGs)
      • Prostacyclin (PGI2)
    • Leukotrienes (LTs) and lipoxins (LXs)
  • Receptor names: Receptor classification system uses the distinguishing letter of the prostanoid (e.g., “E” in prostaglandin E) and combines it with the letter “p” for prostanoid. (e.g., PGE has EP receptors). Subscript numerals represent the subtypes (e.g., PGE2 = EP2). 


  • Eicosanoids are typically not stored within cells.
  • Synthesis is on-demand and is affected by physical, chemical, and hormonal stimuli.
  • With proper stimuli, specific pathways are triggered to produce different eicosanoid families.
  • Stimuli → phospholipases activated → arachidonic acid is released
  • Arachidonic acid is metabolized by different enzyme pathways:
    • LOX → LT and LX
    • COX → cyclization to PGI2, PG, or TXA2
      • COX-1: enzyme constitutively expressed in many tissues
      • COX-2: enzyme induced by pro-inflammatory cytokines and found in the brain, kidney, bone, and female reproductive system
Schematic overview of eicosanoids biosynthesis

Schematic overview of eicosanoid biosynthesis:
Arachidonic acid released from membrane phospholipids by cytosolic phospholipase A2 can be enzymatically converted either to prostaglandins (PGs) and thromboxane (TXA2) by COX enzymes or to leukotrienes (LTs) and lipoxins (LXA4s) by lipoxygenases (LOXs).
5-LOX: 5-lipoxygenase
12/15-LOX: 12/15-lipoxygenase
LTC4S: LTC4 synthase
PGIS: PGI or prostacyclin synthase
PGDS: PG D2 synthase
PGFS: PG F synthase
PGES: PG E synthase
TXAS: TXA2 synthase

Image: “Schematic overview of eicosanoid biosynthesis” by Debeuf N et al. License: CC BY 4.0



  • Metabolite of arachidonic acid synthesized in platelets 
  • Generated through the following process:
    • Arachidonic acid → prostaglandin H2 (PGH2) via enzymes COX-1/COX-2 
    • TXA2 is predominantly COX-1 derived.
    • PGH2→ TXA2 via the action of TXA2 synthase (TXAS) 
  • Receptors: TPɑ and β (expressed in different tissues and cells including platelets, vascular endothelial cells, lungs, kidneys, heart, thymus, and spleen)


  • Activates phospholipase A2
  • Platelet activation:
    • Platelet aggregation
    • Platelet shape change
    • Platelet degranulation of dense granules and alpha granules
  • Vasoconstriction

Clinical correlation

Inflammatory effects of TXA2 in some conditions:

  • Thrombosis:
    • Increased levels of TXA2 are noted in injury and inflammation.
    • ↑ Platelets activation, aggregation, and vasoconstriction → thrombosis
    • Conditions related to thrombosis:
      • Myocardial infarction and angina
      • Atherosclerosis
  • Asthma: TXA2 is related to bronchoconstriction and airway remodeling.



  • Produced from arachidonic acid via COX
    • Basal amounts of PGs are produced through the action of COX-1.
    • Mediators (e.g., cytokines) induce the COX-2 isoform → ↑ PG production
  • Arachidonic acid → PGH2 (common substrate for TXA2 and PGs)
  • From PGH2, different enzymes produce varying PGs.
    • Names of PGs are based on structural features, coded by a letter (e.g., PGD, PGE, PGI).
    • Subscript numeral indicates the number of double bonds (e.g., PGE1, PGE2).
  • Receptors:
    • Prostaglandin E (PGE): E-type prostanoid (EP) 1–4 receptors
    • Prostaglandin D2 (PGD2): D-type prostanoid (DP) 1 and 2 receptors
    • Prostaglandin F2ɑ (PGF2ɑ): F-type prostanoid (FP) receptors
    • PGI2: I-type prostanoid (IP) receptors


Table: Effects of prostaglandins
PGD2 (made predominantly by mast cells)
  • Vasodilation
  • Chemotaxis
  • Vasodilation
  • ↓ Production of gastric acid
  • Uterine contraction (↑ tone)
  • Vasodilation
  • Inflammation:
    • Pain (hyperalgesic)
    • Arterial dilatation (redness)
    • Swelling (↑ microvascular permeability)
  • Uterine contraction (↑ tone in low concentrations)
  • Uterine contraction (↑ tone)
  • Relaxation of ciliary muscle
PGI2 (produced by vascular wall endothelial cells)
  • Vasodilation
  • Inhibitor of platelet aggregation
  • Potentiates effects (↑ permeability and chemotaxis) of other mediators

Clinical correlation

With multiple biologic effects, several PGs have clinical uses:

  • PGE1 (alprostadil) has smooth muscle relaxing effects utilized in:
    • Erectile dysfunction 
    • Preventing closure of patent ductus arteriosus in neonates with congenital heart disease awaiting corrective cardiac surgery
  • PGE1 (misoprostol):
    • Cytoprotective effect used in preventing peptic ulcer
    • Labor induction 
    • Termination of pregnancy (combined with mifepristone (RU-486))
    • Side effect: diarrhea
  • PGE2 (dinoprostone):
    •  Labor induction (cervical ripening)
    • Termination of pregnancy
  • PGF2α:
    • Carboprost (PGF2α analog)
      • Termination of pregnancy
      • Oxytocic effect used in refractory postpartum hemorrhage
    • Latanoprost (topically active PGF2α analog): ↓ intraocular pressure in open-angle glaucoma or ocular hypertension
  • PGI2 (with powerful vasodilating effect): Epoprostenol, treprostinil, iloprost are used for pulmonary hypertension.

Leukotrienes and Lipoxins


  • End-products of the LOX pathway
  • Arachidonic acid is converted to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) by 5-LOX.
    • 5-HPETE → 5-hydroxyeicosatetraenoic acid (5-HETE) → leukotriene A4 (LTA4)
    • By the action of LOX, LTA4 is converted to LTB4, cysteinyl LTs (LTC4, LTD4, LTE4) or LX.
    • In some cells utilizing different LOX pathways, arachidonic acid can be converted to LXs without conversion to LTA4.
  • Receptors:
    • Cysteinyl leukotrienes: CysLT receptors
    • LTB4: leukotriene B (BLT) receptors


Leukotrienes mediate allergic and inflammatory responses with release stimulated by allergens.

Table: Effects of eicosanoids
  • ↑ Vascular permeability
  • Bronchoconstriction
  • Vasoconstriction
LTB4 (and HETE)
  • Leukocyte adhesion
  • Chemotaxis (neutrophils and eosinophils)
LXs A4 and B4
  • Anti-inflammatory
  • Inhibit leukocyte adhesion and chemotaxis

Clinical correlation

Leukotrienes are released from cells and their Inflammatory effects are seen in asthma and allergies.

  • Cysteinyl LTs:
    • Formed from eosinophils and mast cells, which are commonly associated with asthma
    • ↑ Mucus production
    • Bronchoconstriction (smooth muscle contraction)
  • While less well-defined in asthma, LTB4 is a chemoattractant for both neutrophils and eosinophils.

Inhibitors of the Arachidonic Pathway

Inhibition of the pathways, which reduces the production of eicosanoids, also has clinical uses.

  • Corticosteroids: exert anti-inflammatory effects by inhibiting phospholipase A2, blocking the release of arachidonic acid
  • Non-selective COX inhibitors: 
    • ↓ Eicosanoid synthesis → ↓ pain and inflammation 
    • Interferes with gastroduodenal protection (which occurs through COX-1)
    • + Risk of bleeding (due to inhibition of thromboxane synthesis → ↓ platelet aggregation)
    • Include:
      • NSAIDs: reversibly bind COX 
      • Aspirin: irreversibly binds COX and is used against vascular thrombotic events due to its role in reducing TXA2 
    • COX-2 inhibitors:
      • Minimal platelet effects (as the TXA2 pathway is not affected)
      • Fewer GI complications compared with non-selective COX inhibitors
  • LT receptor antagonists
    • Inhibit leukotriene (LT) D4 receptors and LTE4 receptors
    • Zafirlukast, montelukast 
    • Used in exercised-induced bronchospasm, asthma, and allergies
  • LT synthesis inhibitor or 5-LOX inhibitor (zileuton)
    • Selective inhibition of 5-LOX (thus preventing conversion of arachidonic acid to LTs)
    • Used in exercised-induced bronchospasm, asthma, and allergies


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