Topic 86 - Eicosanoids

Question 1

Words to include

Answer 1

• Autacoids
  
  • Eicosanoids
  • Peptides
• Inflammation
• Reproduction
• Eicosanoid synthesis
  
  • 20-carbon fatty acid
  • Phospolipids
  • G protein
  • PLA2 enzyme
  • PLA2 substrate
  • MPL (Membrane Phospholipids)
  • HPETE
  • Lipoxins
  • HETE
  • Leuckotriens
  • Phospholipase A2
  • Arachidionic acid
  • Epoxigenase
  • Cyclooxygenase
  • PGG₂
  • Peroxidase
  • PGH₂
  • Thromboxane
    
    • TXA₂
    • TXB₂
  • Endoperoxidase isomerase
    
    • PGD₂
    • PGF2alpha
    • PGE₂
  • _​Prostacyclin synthease
    
    • Prostzcyclins PGI
  • Lipoxygenase
  • HPETE
    
    • LX
  • Peroxidase
  • HETE
    
    • LT
• Act locally
• Paracrine way
• Lipid soluble
  
  • Surface membrane receptors
  • G protein dependent transduction
• Increasing inflammation
  
  • ​Arachidionic acid
  • Prostaglandins
  • Leukotrienes
  • Vasodilation
  • Chromotaxis
  • Neutrophilic enzyme activation
  • Ca-permability ↑
  • Bronchial contraction
  • Interleukin-1 (fever)
• Insulin release
  
  • Islet cells
  • Paracrine autocrine effects
  • Arachidionic acid
  • Cyclooxygenase
    
    • PGE₂
  • Lipoxygenase
    
    • HPETE
  • Insulin
• Bone resorption
  
  • PGE2
  • Osteoblast
  • Parathyroid hormone-like effect
  • Calcium mobilization
  • Calcium permability ↑
  • Osseous interstitial side
  • Plasma
  • Arachidionic acid
• Reproduction
  
  • Luteolysis
  • PGF_2α
  • Uteurs
  • A. ovarica
  • V. uterina
  • Ovary
• Thrombocyte aggregation
  
  • Endothelial cells
  • Prostacyclins (PGI) nitrogen monoxide
  • G protein
  • cAMP
  • Phospholipase A2
  • Thromboxane synthesis (ø)
  • Platelet aggregation (ø)
  • TXA2
  • Aggregation ↑
  • Arachidionic acid
  • Autocrine potentiation
• Kidney
  
  • Arachidionic acid
    
    • PGE₂
    • PGI₂
  • Tubule cell
  • Renin secretion ↑
  • RPF ↑
  • Effectiveness of ADH ↓
• Regulation
  
  • Phospholipase A2
    
    • Corticoids
  • Cyclooxygenase
    
    • Salicylic acid
    • Indomethacin
    • Ibuprofen
  • Peroxidase
  • Thromboxane synthease
    
    • Benzidamine
    • Imidazol
  • Endoperoxidase
  • Prostacyclin synthease
  • MPL
  • Arachidionic acid
  • PGG₂
  • PGH₂
  • TXB₂
  • TXA₂
  • PGD₂
  • PGF_2α
  • PGE₂
  • Prostacyclins PGI

Question 2

Topics to include in the essay

Answer 2

1. Autacoids
   
   • Eicosanoids
   • Peptides
2. Eicosanoid synthesis
3. Effects of eicosanoids
   
   • Increasing inflammation
   • Insulin release
   • Bone resorption
   • Reproduction
   • Thrombocytte aggregation
   • Kidney
4. Regulation

Question 3

General characteristics of eicosanoids

Answer 3

• Eicosaoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids with 20-carbon length
• They act locally or through a paracrine way
• Lipid soluble
  
  • ​But they bind to surface membrane receptors and elicit G protein dependent transduction

Question 4

Which group does eicosanoids belong to?

Answer 4

• Autacoids can be divided into:
  
  1. Eicosanoid
     
     • Produced everywhere in the body, by all cells
  2. Peptides

Question 5

Eicosanoid synthesis

Answer 5

• Eicosanoids are 20-carbon fatty acids
  
  • Synthesized as final products of controlled, enzymatic steps initiated from phospholipid
• Mediated by G protein → activates PLA2 enzyme
  
  • MPL (Membrane Phospholipoids) = PLA2 substrates
• HPETE: Hydroxy-peroxy-eicosa-tetraenoic-acid
• Lipoxins: 3 OH group, 4 double bonds
• HETE: Hydroxy-eicosa-tertaenoic-acid
• Leuckotriens: effective when bound to proteins in peptide-LT form

Question 6

Effects of eicosanoids

Answer 6

1. Inflammation increasing effect
2. Insulin release from islet cells
3. Bone resorption: equlpotent with PTH
4. Stimulation of luteolysis (reproduction)
5. Thrombocyte aggregation
6. Kidney

Question 7

Effects of eicosanoids

Inflammation increasing effect

Answer 7

• Prostaglandins and leukotrienes initiate inflammation
• Result:
  
  • Vasodilation
  • Chemotaxis
  • Neutrophilic enzyme activation
  • Ca-permabillity ↑
  • Bronchial contraction
  • Interleukin-1 - fever

Question 8

Effects of eicosanoids

Insulin release

Answer 8

• Insulin release from islet cells
• HPETE stimulates PGE2 inhibits insulin release by B cells

Question 9

Effects of eicosanoids

Bone resorption

Answer 9

• Bone resorption: equipotent with PTH
• PGE2 (from the osteoblast) has a parathyroid hormone-like effect on calcium mobilization from the bone:
  
  • Increases calcium permeability in the osseous interstitial side, making possible the entry of calcium into the plasma

Question 10

Effects of eicosanoids

Reproduction

Answer 10

• Stimulation of luteolysis
• Precondition of luteolysis during cycle is the PGF_2α production of the uterus
• Twisted a. ovarica and v. uterina makes possible for the diffusion of PGF_2α into the ovary before it could be degraded in the circulation because of staying there too long

Question 11

Effects of eicosanoids

Thrombocyte aggregation

Answer 11

1. Endothelial cells (in mouse) release prostacyclins (PGI) nitrogen monoxide, and induce G protein mediated increase of cAMP
2. IC cAMP inhibits the enzyme phospholipase A2
   
   • Ø thromboxane synthesis → Ø platelet aggregation
3. TXA2 synthesis in platelets increases aggregation

Question 12

Effects of eicosanoids

Kidney

Answer 12

1. Prostacyclin synthesis in renal tubule cells enhances renin secretion
2. Increases RPF
3. Antagonizes the effect of ADH

• Result:
  
  • Renin secretion ↑
  • PRF ↑
  • Effectiveness of ADH ↑

Question 13

Regulation of eicosanoids

Answer 13

• Corticosteroids, meepacrine inhibit the entire eicosanoid synthesis
  
  • Due to anti-inflammatory effect of glucocorticoids
• Inhibits cyclooxygenase:
  
  • ​Salicyclic acid
  • Indomethacin
  • Ibuprofen
• Inhibits thromboxane synthease:
  
  • ​Benzidamine
  • Imidazol