Eicosanoid Signaling

Question 1

Describe Eicosanoids

Answer 1

Derived from fatty acids containing 20 carbons; Act primarily on cells nearby to those that secreted them (Auto/Paracrine)

Question 2

What are the steps in eicosanoid hormone action?

Answer 2

1. Liberation of membrane phospholipids
2. Cyclo vs lipooxygenase pathways
3. Actions of synthases
4. Binding and activity of receptors.

Question 3

What does phospholipase A2 do?

Answer 3

It liberates the fatty acid from C2 of membrane phospholipid; Making arachodonic acid

Question 4

What regulates phospholipase A2?

Answer 4

Positive: Thrombin
Negative: Anti-inflammatory corticosteriods

Question 5

Discuss the lipoxygenase pathway

Answer 5

Leads to 2 compounds,

1. Lipoxins
2. Leukotrienes; 3 conjugated double bonds.

Question 6

Discuss the cyclooxygenase pathway

Answer 6

Inhibited by aspirin. Two types of compounds

1. Prostaglandins; 20 carbon FAs with a 5 carbon ring
2. Thromboxane; 6 membered ether ring.

Question 7

Discuss PGI2

Answer 7

Made by endothelial cells; Vasodilation, inhibits platelet aggregation and augments the effects of Nitric Oxide (Also produced by endothelial cells).

Question 8

Discuss TxA2

Answer 8

Made by platelets; Vasoconstriction, promotes platelet aggregation and augments the effects of Thrombin (Made by liver)

Question 9

How are prostaglandins cytoprotective from HCl in the intestine?

Answer 9

Gastroduodenal mucosa makes PGE2 which binds to its receptor, inhibits cAMP increase and HCl secretion; Also stimulates HCO3- secretion.

Question 10

What are the anti-inflammatory endogenous agents?

Answer 10

Anti-inflammatory lipoxins, resolvins, and protectins

Question 11

Compare Cox 1 to Cox 2

Answer 11

Cox1 performs the constitutive houskeeping function in the GI tract and vascular homeostasis.
Cox2 produces an inducible inflammatory response.

Question 12

Compare the efficacy of low and high dose aspirin, 6-MNA, and celecoxib on Cox 1 and 2

Answer 12

Low dose aspirin: Works better on Cox 1
High dose aspirin: Works equally on both
6-MNA: Works better on Cox 2 than 1
Celecoxib: Works much stronger on 2 than on 1

Question 13

How do the different leukotrienes differ?

Answer 13

Produced by Glutathione S-transferase allows LTC4 to leave the cell and cleave off amino acids to yield LTD4 and LTE4; They have different amino acids attached.

Question 14

What do these leukotrienes do?

Answer 14

Cause slow sustained smooth muscle contraction in the airways; Much more potent than histamine. LTC,D,E4

Question 15

How are resolvins made?

Answer 15

1. EPA is converted into HEPE by cytochrome p450 monoxygenase inside an endothelial cells. Also works with Cox 2
2. HEPE is taken up by PMNs and converted to resolvins.